Lower numbers of circulating Natural Killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease.

Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

Diet quality of persons living with HIV/AIDS on highly active antiretroviral therapy.

BACKGROUND: This study sought to assess the diet quality of individuals living with HIV/AIDS who were receiving antiretroviral therapy in São Paulo, Brazil. METHODS: This cross-sectional study involved 56 HIV-infected adults. Demographic and anthropometric data were collected, and diet quality was measured using the Healthy Eating Index (HEI), modified for Brazilians, which included ten components: adequacy of intake of six different food groups, total fat, cholesterol, dietary fibre and dietary variety. RESULTS: Among the individuals assessed, 64.3% of the participants had a diet needing improvement, while 8.7% had a poor diet. The overall HEI score was 68.3 points (SD = 14.9). Mean scores were low for fruits, vegetables, dairy products and dietary fibre; and high for meats and eggs, total fat and cholesterol. The overall HEI score was higher among individuals who were not overweight (P = 0.003), who were also more likely to achieve dietary goals for dairy products (P = 0.039) and grains (P = 0.005). CONCLUSION: Most of these adults living with HIV/AIDS had diets that required improvement, and being overweight was associated with poorer diet quality. Nutritional interventions aimed at maintaining healthy body weight and diet should be taken into account in caring for HIV-infected people.

Sexual abuse victimisation and perpetration in a cohort of men living with HIV/AIDS who have sex with women from São Paulo, Brazil.

Sexual abuse leads to physical harm and devastating psychosocial consequences. It increases risk of HIV transmission and is associated with risky behaviour. Little is known about sexual abuse victimisation (SAV) and perpetration (SAP) among HIV-positive men who have sex with women (MSW). We investigated self-reported SAV and SAP among 242 Brazilian MSW selected at HIV care centres. Patients were questioned about sociodemographic data, mode of HIV acquisition, sexual practices, drug use and history of SAV or SAP. Prevalence of outcomes was estimated and risk factors for SAP investigated by logistic regression. Fifty-eight (24.1%) interviewees reported SAV. Of patients abused before 15 years of age, 64.3% reported events before the age of ten. Aggressors included relatives, friends and teachers. Among those victimised after 15 years old, 57.7% described events before 17 and 38.5% had acquainted aggressors. Fourteen (5.8%) interviewees reported SAP and most knew their victims. Sexual abuse perpetration was associated with lower schooling, marital status, illicit drug use and self-reported SAV. Sexual abuse was frequently reported by MSW from this cohort. Identifying predictors of violence and addressing SAV and SAP in comprehensive HIV care may help reduce violent behaviour, psychological distress and contribute to maximise benefits of preventive and care interventions.

Sexual abuse victimisation and perpetration in a cohort of men living with HIV/AIDS who have sex with women from São Paulo, Brazil

Sexual abuse leads to physical harm and devastating psychosocial consequences. It increases risk of HIV transmission and is associated with risky behaviour Little is known about sexual abuse victimisation (SAV) and perpetration (SAP) among HIVpositive men who have sex with women (MSW). We investigated self-reported SAV and SAP among 242 Brazilian MSW selected at HIV care centres. Patients were questioned about sociodemographic data, mode of HIV acquisition, sexual practices, drug use and history of SAV or SAP. Prevalence of outcomes was estimated and risk factors for SAP investigated by logistic regression. Fifty-eight (24.1%) interviewees reported SAV. Of patients abused before 15 years of age, 64.3%reported events before the age of ten. Aggressors included relatives, friends and teachers. Among those victimised after 15 years old, 57.7 described events before 17 and 38.5 had acquainted aggressors. Fourteen (5.8%) interviewees reported SAP and most knew their victims. Sexual abuse perpetration was associated with lower schooling, marital status, illicit drug use and self-reported SAV. Sexual abuse was frequently reported by MSW from this cohort. Identifying predictors ofviolence and addressing SAVand SAP in comprehensive HIV care may help reduce violent behaviour, psychological distress and contribute to maximise benefits of preventive and care interventions

Sexual abuse victimisation and perpetration in a cohort of men living with HIV/AIDS who have sex with women from São Paulo, Brazil

Sexual abuse leads to physical harm and devastating psychosocial consequences. It increases risk of HIV transmission and is associated with risky behaviour Little is known about sexual abuse victimisation (SAV) and perpetration (SAP) among HIVpositive men who have sex with women (MSW). We investigated self-reported SAV and SAP among 242 Brazilian MSW selected at HIV care centres. Patients were questioned about sociodemographic data, mode of HIV acquisition, sexual practices, drug use and history of SAV or SAP. Prevalence of outcomes was estimated and risk factors for SAP investigated by logistic regression. Fifty-eight (24.1%) interviewees reported SAV. Of patients abused before 15 years of age, 64.3%reported events before the age of ten. Aggressors included relatives, friends and teachers. Among those victimised after 15 years old, 57.7 described events before 17 and 38.5 had acquainted aggressors. Fourteen (5.8%) interviewees reported SAP and most knew their victims. Sexual abuse perpetration was associated with lower schooling, marital status, illicit drug use and self-reported SAV. Sexual abuse was frequently reported by MSW from this cohort. Identifying predictors ofviolence and addressing SAVand SAP in comprehensive HIV care may help reduce violent behaviour, psychological distress and contribute to maximise benefits of preventive and care interventions

Sexual orientation, use of drugs and risk perception among HIV-positive men in Sao Paulo, Brazil.

The aim of this cross-sectional study, carried out among 250 HIV-positive (HIV+) men who have sex with women, was to describe their risk perception before learning of their HIV+ status and their sexual and drug use behaviour. Of the 250 men, 62.0% were heterosexuals and 38.0% where bisexuals. They most often reported becoming infected through unprotected sex (24.5%) and injecting drug use (11.0%). They were usually tested because they became ill (42.2%). Condom use with women in all episodes of sexual intercourse before HIV+ diagnosis was reported by 22.6% of heterosexuals and 34.7% of bisexuals (P < 0.05). With respect to drug use, 58.0% reported the use of drugs at some period in their lifetime. A higher proportion of individuals who had used drugs perceived themselves at risk (P < 0.05). Findings showed that most HIV+ men who have sex with women, regardless of sexual orientation or injecting drug use, did not use condoms and did not perceive themselves at risk before learning of their HIV+ status, and only undergo testing due to illness. The implications for heterosexual transmission of HIV are discussed.

Randomized trial with itraconazole, ketoconazole and sulfadiazine in paracoccidioidomycosis.

Forty-two patients with active paracoccidioidomycosis were randomized to receive itraconazole (50-100 mg d(-1)), ketoconazole (200-400 mg d(-1)) or sulfadiazine (100-150 mg kg d(-1) up to 6 g d(-1)) for 4-6 months, followed by slow release sulfa until negativity of serological tests. All 14 patients in itraconazole and sulfadiazine groups and 13 in the ketoconazole group showed an adequate clinical response to the chemotherapy. One patient in the latter group showed treatment failure according to clinical and mycological criteria. The test of the hypothesis that the drugs reduced antibody levels up to ten months of treatment showed a p value equal to 0.0001 for itraconazole, 0.017 for ketoconazole and 0.0012 for sulfadiazine; this reduction was similar for the three groups. In this first randomized study for the treatment of paracoccidioidomycosis we could not show superiority of any one regimen over the others in the clinical and serological responses of patients with the moderately severe form of the disease.

Interleukin-1 receptor antagonist gene polymorphism and circulating levels of human immunodeficiency virus type 1 RNA in Brazilian women.

Interleukin-1 receptor antagonist (IL-1ra) gene polymorphisms in 83 human immunodeficiency virus (HIV)-seropositive women were evaluated. Fourteen of the subjects (16.9%) were homozygous for IL-1ra allele 2 (IL-1RN*2). These women had a lower median level of HIV RNA than did women homozygous for allele 1 (IL-1RN*1) (P = 0.01) or heterozygous for both alleles (P = 0.04). Among 46 subjects not receiving antiretroviral treatment, HIV levels were also reduced in IL-1RN*2 homozygous individuals (P < 0.05). There was no relation between IL-1ra alleles and CD4 levels.

HTLV-1 and HTLV-2 infections in HIV-infected individuals from Santos, Brazil: seroprevalence and risk factors.

Because HTLV-I, HTLV-2, and HIV share identical modes of transmission, simultaneous or subsequent infections with these retroviruses are to be expected. The population of Santos, the largest port in Latin America, includes large numbers of female commercial sex workers and intravenous drug users, presumably having been exposed to retroviral infection. To evaluate the seroprevalence of HTLV infection and their associated risk factors, a cross-sectional survey was carried out in 499 HIV-infected individuals from Santos, Brazil. HTLV testing consisted of enzyme immunoassays for serologic screening and confirmatory Western blot testing. Overall HTLV-I and HTLV-2 seroprevalences were 6.0% (95% confidence interval [CI], 3.9-8.1) and 7.4% (95% CI, 5.1-9.7), respectively. Multivariate logistic regression for statistical analysis revealed HTLV-I infection to be independently associated with: intravenous drug use (IDU) (odds ratio [OR]. 2.99; 95% CI, 1.09-8.20), seropositivity to hepatitis C virus (HCV) (OR, 3.03; 95% CI, 1.02-9.01) and < 3 years of education (OR, 4.73; 95% CI, 1.56-14.41). HTLV-2 infection was associated with: IDU (OR, 3.22; 95% CI, 1.33-7.84), HCV seropositivity (OR, 5.40; 95% CI, 1.86-15.66) and nonwhite race (OR, 3.32; 95% CI, 1.58-7.00). Results indicate that HIV-infected individuals living in Santos are at similarly high risk of being exposed to HTLV-1 and HTLV-2. IDU constitutes the main risk factor for HTLV acquisition in this population, and there is no significant risk associated with sexual practice.

Ureaplasma urealyticum colonization in the vaginal introitus and cervix of human immunodeficiency virus-infected women.

Ureaplasma urealyticum colonization was examined in paired cervical and introital specimens from 56 untreated HIV-seropositive women. Specimens were tested for U. urealyticum by polymerase chain reaction (PCR). Peripheral blood was examined for CD4 lymphocyte counts and HIV RNA concentration. U. urealyticum was detected in the cervix of 38 (69.1%) women. Introital U. urealyticum was present in 16 (28.6%) women, all of whom were cervical-positive. Cervical motion pain was present in 40.0% of women with U. urealyticum in the introitus and cervix, 23.8% of those with only cervical U. urealyticum and 5.9% of women negative for this organism (P=0.03). There was no relation between U. urealyticum colonization and CD4 lymphocyte count. However, 64.3% of women with introital U. urealyticum had circulating HIV RNA levels > 10,000 copies per ml as compared with 28.6% of women with only cervical U. urealyticum and 7.1% of women negative for this organism (P < 0.01).

Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method.

From March 1996 to August 1997, a study was carried out in a malaria endemic area of the Brazilian Amazon region. In vivo sensitivity evaluation to antimalarial drugs was performed in 129 patients. Blood samples (0.5 ml) were drawn from each patient and cryopreserved to proceed to in vitro studies. In vitro sensitivity evaluation performed using a radioisotope method was carried out with the cryopreserved samples from September to December 1997. Thirty-one samples were tested for chloroquine, mefloquine, halofantrine, quinine, arteether and atovaquone. Resistance was evidenced in 96.6% (29/30) of the samples tested for chloroquine, 3. 3% (1/30) for quinine, none (0/30) for mefloquine and none for halofantrine (0/30). Overall low sensitivity was evidenced in 10% of the samples tested for quinine, 22.5% tested for halofantrine and in 20% tested for mefloquine. Means of IC 50 values were 132.2 (SD: 46. 5) ng/ml for chloroquine, 130.6 (SD: 49.6) ng/ml for quinine, 3.4 (SD: 1.3) ng/ml for mefloquine, 0.7 (SD: 0.3) ng/ml for halofantrine, 1 (SD: 0.6) ng/ml for arteether and 0.4 (SD: 0.2) ng/ml for atovaquone. Means of chloroquine IC 50 of the tested samples were comparable to that of the chloroquine-resistant strain W2 (137.57 ng/ml) and nearly nine times higher than that of the chloroquine-sensitive strain D6 (15.09 ng/ml). Means of quinine IC 50 of the tested samples were 1.7 times higher than that of the low sensitivity strain W2 (74.84 ng/ml) and nearly five times higher than that of the quinine-sensitive strain D6 (27.53 ng/ml). These results disclose in vitro high resistance levels to chloroquine, low sensitivity to quinine and evidence of decreasing sensitivity to mefloquine and halofantrine in the area under evaluation.

In vivo efficacy of mefloquine for the treatment of Falciparum malaria in Brazil.

Ninety-four patients with falciparum malaria were treated with mefloquine (1000-mg single dose) and remained hospitalized in a malaria-free area for a minimum of 28 days. There was 1 parasitologic failure (grade I resistance [RI]) for a 99% cure rate (95% confidence interval, 94.2%-99.7%). Mean parasite clearance time by thick smear was 45.7 h (SD, 11.4 h). The subject in whom therapy failed had a parasite clearance time (71 h) >2 SD above the population mean. His plasma mefloquine level 48 h after administration was lower (578 ng/mL) than the range of levels from 8 randomly selected cured subjects (834-2360 ng/mL). The IC50 to mefloquine for the recrudescent strain of the RI failure was in the upper 90th percentile of IC50 values from 30 cured subjects. These results show a high mefloquine cure rate but document the onset and mechanism of the emergence of resistance.

Tumores neuro-endocrinos do estomago e duodeno: estudo morfologico e imunohistoquimico das suas diferentes formas de apresentacao clinico-patologicas / Neuroendocrine tumors of the stomach and duodenum: a morphologic and imunohistochemical study of the different clinical and pathological presentations

Apos o advento da endoscopia digestiva alta, o numero de casos diagnosticados com tumores neuroendocrinos (TNE) gastricos e duodenais tem aumentado consideravelmente. Novas classificacoes tem sido propostas, entretanto ha escassez de conhecimento em nosso meio, motivando o presente estudo...

Human T-cell lymphotropic virus type 1 infection and ocular manifestations in São Paulo, Brazil.

OBJECTIVES: Although human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis has been well recognized in Japan, related studies in Brazil are scarce. We performed a serologic survey for HTLV-1 infection among patients with uveitis and investigated the ocular findings in HTLV-1-asymptomatic carriers. METHODS: One hundred ninety serum samples from patients with uveitis of determined (n = 137) and undetermined origins (n = 53) being examined at the Uveitis Service, University of São Paulo, São Paulo, Brazil, underwent testing using HTLV enzyme-linked immunosorbent assay and discriminatory Western blots. One hundred five asymptomatic blood donors and/or their relatives who were seropositive for HTLV-1 (carrier group) and 105 age- and sex-paired blood donors who were seronegative for HTLV-1 (control group) underwent ocular evaluation. For the statistical analysis, chi2 test was used. RESULTS: Only 1 patient with uveitis was seropositive for HTLV- 1, and she belonged to the group with uveitis of undetermined origin. Results of tear films were evaluated in 52 carriers. The prevalence of a decreased tear break-up time was significantly higher in the carrier compared with the control group (P = .02). Two carriers had keratoconjunctivitis sicca. Three of the 105 carriers exhibited mild uveitis (cells in the vitreous, retinal and choroidal infiltrates, retinal vasculitis, and bilateral pars planitis). Retinal pigmentary changes were found in both groups (no statistical difference). CONCLUSIONS: Early tear abnormalities may be present in asymptomatic carriers, and mild uveitis may be found among them. The relatively low seroprevalence of HTLV-1 in the Brazilian population made it difficult to establish the real importance of HTLV-1-associated uveitis among our patients with uveitis.

Molecular detection and isolation of human T-cell lymphotropic virus type I (HTLV-I) from patients with HAM/TSP in São Paulo, Brazil.

BACKGROUND: Infection with HTLV-I is etiologically linked with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However some patients with chronic progressive paraparesis resembling HAM/TSP have been shown to be infected with HTLV-II. OBJECTIVE: To clarify the role of each of these human retroviruses in the etiology of HAM/TSP in São Paulo, Brazil. STUDY DESIGN: A detailed serological and molecular analysis of HTLV-I/II infection was performed in a cohort of 19 patients with HAM/TSP attending a neurological clinic. RESULTS: Plasma samples analyzed for anti-HTLV-I/II antibodies using a Western blot assay, comprising HTLV-I (rgp46I)- and HTLV-II (rgp46II)-specific recombinant env epitopes, demonstrated reactivity to rgp46I and hence were typed as seropositive for HTLV-I. Presence of HTLV genomic sequences in peripheral blood mononuclear cells (PBMC) was sought after by PCR using consensus primers SK 110 and SK 111 for the pol region of HTLV proviral DNA followed by hybridization with type-specific probes--SK 112 (HTLV-I) and SK 188 (HTLV-II). Southern blots from all individuals hybridized with SK 112 but not with SK 188, further confirming HTLV-I infection. Cocultivation of PBMC from eight of these patients with activated lymphocytes from normal individuals resulted in active viral production, detected as presence of soluble p24gag antigen in culture supernatants. Investigation of risk factors for HTLV-I infection in these individuals revealed that five out of 19 patients studied (26.3%) had received blood transfusions previous to disease onset.

Laboratory characterization of human T cell lymphotropic virus types 1 (HTLV-1) and 2 (HTLV-2) infections in blood donors from Sao Paulo, Brazil.

Serologic screening for human T cell lymphotropic virus types 1/2 (HTLV-1/2) infection in blood donors has been recently introduced in Brazil. Analysis of 351,639 blood donations in Sao Paulo from January 1992 to October 1993 identified 1,063 positive (0.30%) and 2,238 indeterminate (0.63%) samples based on serologic confirmation using a 21e Western blot. A detailed analysis (serologic, molecular, and virologic), based on a laboratory diagnostic algorithm for characterization of HTLV-1 and HTLV-2 infections was undertaken in 50 seropositive or seroindeterminate blood donors. Modified serologic assays (2.3 Western blot that incorporate type-specific recombinant peptides) performed in 29 HTLV-1/2 positive and 21 HTLV-1/2 indeterminate donors with the 21e Western blot identified 25 as infected with HTLV-1, four with HTLV-2, five with untypable HTLV-1/2, 15 as HTLV-1/2 indeterminate, and one as seronegative. Polymerase chain reaction (PCR) analysis using DNA amplification of proviral pol and tax sequences from peripheral blood mononuclear cells confirmed HTLV-1 and HTLV-2 infections in all 2.3 Western blot seropositive donors; of the five serologically untypable donors, three were confirmed to be HTLV-1 positive, one HTLV-2 positive, and one negative by PCR. All of the seroindeterminate donors were also negative by PCR. Furthermore, HTLV-1 could be isolated in cocultures from 10 of 18 infected donors. Cell lines developed from two HTLV-1-infected donors were of T cell phenotype (CD2+, CD3+), exhibiting surface markers of activated CD4 cells (CD4+ CD25+ HLA-DR+). Thus, we provide evidence for the high seroprevalence of HTLV infection in blood donor population in Sao Paulo, Brazil compared with North American donors and propose a comprehensive serologic and genotypic diagnostic algorithm for HTLV-infected donors that has strong implications for counseling of these individuals.

PIP: Blood donors in Brazil have recently begun to be screened for infection with HTLV types 1 and 2. Of 351,639 blood donations screened in Sao Paulo from January 1992 to October 1993, 1063 positive and 2238 indeterminate samples were identified based upon serologic confirmation using the 21e Western blot. Detailed serologic, molecular, and virologic analysis, based upon a laboratory diagnostic algorithm for the characterization of HTLV-1 and HTLV-2 infections, was conducted upon 50 seropositive or seroindeterminate blood donors. 2.3 Western blot serologic assays, which incorporate type-specific recombinant peptides, performed in 29 HTLV 1/2 positive and 21 HTLV 1/2 indeterminate donors with the 21e Western blot identified 25 as infected with HTLV-1, 4 with HTLV-2, 5 with untypeable HTLV 1/2, 15 as HTLV 1/2 indeterminate, and 1 as seronegative. Polymerase chain reaction (PCR) analysis using DNA amplification of proviral pol and tax sequences from peripheral blood mononuclear cells confirmed HTLV-1 and HTLV-2 infections in all 2.3 Western blot seropositive donors. Of the 5 serologically untypeable donors, 3 were found to be HTLV-1-positive, 1 HTLV-2-positive, and 1 negative by PCR. All seroindeterminate donors were also negative by PCR. HTLV-1 could be isolated in cocultures from 10 of 18 infected donors.