High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil

In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29%, HIV-1 B in 22.6% and, the recently identified CRF31_BC, in 23.4% of 128 volunteers. Other variants were HIV-1 F in 10% and other mosaics in 5.5%. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

Frequency of hepatitis B immunity and occupational exposures to body fluids among brazilian medical students at a public university

In the present study the frequencies of immunity against hepatitis B (HB) and of potentially contaminating accidents among medical students of a Brazilian public university were evaluated. Of all the 400 students who should have been immunized, 303 (75.7%), 66.3% of whom were women, answered an anonymous, self-administered questionnaire. Serum anti-HBs were determined in 205 of them and titers > 10 UI/L were considered to be protective. A total of 86.8% of students had received three doses of HB vaccine. The frequency of immunity among women (96.4%) was higher (p = 0.04) than that among men (87.7%). Among those who did not have immunity, 12/13 (92.3%) had been vaccinated before entering medical school. Only 11% of the students with complete vaccination had previously verified serological response to the vaccine. A total of 23.6% reported having been somehow exposed to blood or secretions. Among final-year students, this frequency was 45.0%, being similar among men (47.8%) and women (43.2%). Of all these accidents, 57.7% were due to body fluids coming in contact with mucosa and 42.3% due to cut and puncture accidents. The results from this study show that: 1) the frequency of immunity against HB is high among the evaluated medical students, although verification of response to vaccination is not a concern for them; 2) anti-HBs titers should be verified after complete vaccination and on a regular basis, especially by men; and 3) the frequency of potentially contaminating accidents is high.

TEMPORAL TRENDS IN THE DETECTION RATES OF HEPATITIS B IN THE SANTA CATARINA STATE, BRAZIL

Hepatitis B is a serious public health problem. The state of Santa Catarina presents areas of high endemicity. The aim of this study was to describe temporal trends in detection rates of hepatitis B in the period from 2002 to 2009 in Santa Catarina and in its regions. A time series study was carried out. Crude rates were calculated and standardized by age using the direct method. Annual variation percentages were estimated by Joinpoint regression. There were two distinct and significant trends in Santa Catarina. From 2002 to 2006 a significant increase of 5.9% per year was observed. From 2006, there was a significant decrease of 6.4% per year. In this same period the southern and far-western regions had significant increases of 15.9% and 4.6% and significant decreases of 7.5% and 4.8%, respectively. Greater Florianópolis and Northeast also showed significant increases until 2006, of 15.4% and 17.4%, respectively. In the following period, non-significant decreases of 5.8% and 9.8% respectively were observed. Foz do Rio Itajaí and Planalto Serrano showed non-significant increases up to half of the studied period of 21.1% and 12.0%, respectively and after, significant decreases of 21.5% and 18.0%, respectively. Vale do Itajaí showed a significant decrease of 9.7%; Planalto Norte showed a non-significant decrease of 0.6% and Midwest a non-significant increase of 2.7% per year, in the period from 2002 to 2009.

HEPATITIS B VACCINATION COVERAGE AND POSTVACCINATION SEROLOGIC TESTING AMONG MEDICAL STUDENTS AT A PUBLIC UNIVERSITY IN BRAZIL

The aim of this cross-sectional study was to determine the hepatitis B vaccination coverage among medical students at a public university in Rio de Janeiro, Brazil, and their compliance with the postvaccination serologic testing recommendations. Of the total of 858 students, 675 (78.7%) participated in the study. Among the participants, 48.9% (95% CI: 45.1% to 52.7%) were vaccinated against hepatitis B (received ≥ 3 doses of the vaccine), 31.6% were not (received 0, 1 or 2 doses), and 19.6% did not know their vaccination status. Hepatitis B vaccination coverage increased from 26.0% among first-year students to 70.6% among sixth-year students while the prevalence of unknown vaccination status decreased from 39.7% among first-year students to 2.4% among sixth-year students. The frequency of unvaccinated students ranged from 23.7% among fifth-year students to 34.4% among first-year students. Only 34.8% of the vaccinated students performed the anti-HBs testing after vaccination. Among these medical students, we found a low adherence to the hepatitis B vaccination and to the postvaccination serologic testing. A comprehensive hepatitis B immunization program should be offered to students at this medical school.

Differential Internalization of Amphotericin B - Conjugated Nanoparticles in Human Cells and the Expression of Heat Shock Protein 70

Although a variety of nanoparticles (NPs) functionalized with amphotericin B, an antifungal agent widely used in the clinic, have been studied in the last years their cytotoxicity profile remains elusive. Here we show that human endothelial cells take up high amounts of silica nanoparticles (SNPs) conjugated with amphotericin B (AmB) (SNP-AmB) (65.4 12.4 pg of Si per cell) through macropinocytosis while human fibroblasts internalize relatively low amounts (2.3 0.4 pg of Si per cell) because of their low capacity for macropinocytosis. We further show that concentrations of SNP-AmB and SNP up to 400 mg/mL do not substantially affect fibroblasts. In contrast, endothelial cells are sensitive to low concentrations of NPs (above 10 mg/mL), in particular to SNP-AmB. This is because of their capacity to internalize high concentration of NPs and high sensitivity of their membrane to the effects of AmB. Low-moderate concentrations of SNP-AmB (up to 100 mg/mL) induce the production of reactive oxygen species (ROS), LDH release, high expression of pro-inflammatory cytokines and chemokines (IL-8, IL-6, G-CSF, CCL4, IL-1b and CSF2) and high expression of heat shock proteins (HSPs) at gene and protein levels. High concentrations of SNP-AmB (above 100 ug/mL) disturb membrane integrity and kill rapidly human cells(60% after 5 h). This effect is higher in SNP-AmB than in SNP.

Estimativa da prevalência de infeccções micobacterianas em escolares na Guanabara, através de testes intradérmicos com PPD-Rt 23 E PPD-B

Foram testados 543 escolares do Estado da Guanabara, Brasil, na faixa etária de 12 a 14 anos, quanto à hipersensibilidade tuberculínica ao PPD-Rt 23 e ao PPD-B. Confirmou-se a alta prevalência de sensibilidade às tuberculoproteínas em crianças, obtendo-se 33,65% de reatores fortes ao PPD-Rt 23. Da população estudada 85,63% reagiu ao PPD-B, sendo que 6,26% apresentou reação maior a esta tuberculina que ao PPD-Rt 23, sugerindo uma hipersensibilização pelo bacilo Battey, ou outra microbactéria mais relacionada antigenicamente a esse microrganismo que ao Mycobacterium tuberculosis.

Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein Levels

Adult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.

Ocorrência de hepatites não-anão-B em unidade de hemodiálise

A monitorização mensal de alanina aminotransferase (ALT) sérica de pacientes em hemodiálise e os testes sorológicos para exclusões de infecções por vírus da hepatite A (HAV), vírus da hepatite B (HBV), citomegalovirus (CMV) e vírus Epstein-Barr (EBV), permitiu-nos identificar 11 casos de hepatites não-A, não-B em 111 indivíduos avaliados durante o período de 12 meses e acompanhados por 2 anos. Foram observados 3 padrões de atividade de ALT: elevação em pico monofásico em 2, bifásico ou polifásico em 6 e em platô em 3 pacientes. Individíduos com padrão monofásico exibiram os níveis mais elevados de ALT. Cinco pacientes apresentaram normalização bioquímica persistente 4,8 meses em média após o início da elevação aguda e seis evoluíram com ascensão crônica de ALT durante o período de estudo. A hepatite não-A, não-B foi, predominantemente, assintomática e anictérica, sempre antecedida por transfusões sangüíneas e com maior incidência nos seis primeiros meses de terapia dialítica dos pacientes.

Rastreamento sorológico para hepatite B em profissionais de saúde na cidade de Goiânia - Goiás

Pesquisou-se marcadores para o vírus da hepatite B em profissionais de saúde, ligados a três instituições na cidade de Goiânia-Goiás. A prevalência da infecção virai encontrada foi de 23,4% em relação aos diferentes marcadores (AgHBs, anti-HBs e anti-HBc). Entre os indivíduos positivos, 2,3% eram portadores do vírus e 21,1% demonstraram infecção prévia. Destes, 9,8% apresentaram como marcador, apenas o anti- HBs e 32,6% o anti-HBc. Dezenove indivíduos relataram vacinação ao vírus, sendo que 8 soroconverteram para o anti-HBs e 6 apresentaram também o anti-HBc, e os demais não apresentaram qualquer marcador virai. A maior prevalência foi a partir dos 30 anos de idade (p< 0,05). O sexo masculino mostrou percentual superior ao feminino, 29,5% e 21,1% respectivamente (p< 0,05). Quando considerada a prevalência virai em relação a contatos com sangue e/ou pacientes, o percentual de positividade para contactantesfoi 25,9% (p < 0,05), e a maior prevalência do vírus ocorreu a partir de 10 anos de trabalho (p < 0,05). A hemodiálise mostrou-se como setor de maior risco cujo percentual foi de 77,0% (p<0,05).

Acute exacerbation in chronic hepatitis B virus infection

A case of an acute exacerbation of liver injury in a chronic HBV infected young male is reported. The correlation between the severe symptomatic hepatitis is done with the histopathologic findings of extense areas of bridging necrosis on the Iwer biopsy. The serological pattern for markers of HBV (HBsAg +, anti HBs g -, HBeAg -, anti HBe +, anti HBcIgG + and IgM -) confirm a chronic infection, ana the authors propose that the episode of severe hepatitis relates to the recent spontaneous seroconvertion of HBe Ag to anti HBe. Other causes of hepatitis were excluded, and the control liver biopsy (6 months later) showed normalization of hepatic architecture and absence of markers of viral replication in tissue and serum. A review of literature is done in an attempt to elucidate the diagnostic possibilities in this case, with emphasis on new immunoassays useful in differentiating between acute hepatitis B and acute exacerbation of a chronic hepatitis by the same virus.

Prevalência dos marcadores sorológicos dos vírus da hepatite B e D em crianças das tribos Caiabietxucarramãe do parque indígena do Xingu, Brasil central

O Parque Indígena do Xingu (PIX) está localizado no estado do Mato Grosso, na região de transição de cenado ao sul e da floresta Amazônica ao norte. Dados de literatura mostram que a população adulta apresenta elevada prevalência de marcadores do vírus da hepatite B (HBV). O presente estudo visa determinar a prevalência dos marcadores do HBV e do HDV na população indígena do PIX de zero a 14 anos, e investigar a forma de transmissão do HBV na região. Entre as 17 tribos existentes no PIX escolheu-se os Caiabi e os Txucairamãe que diferem em seus hábitos de vida e habitam a região Norte do parque com características de clima, vegetação e fauna semelhantes ás da região Amazônica. Avaliaram-se 222 crianças (116 Txucarramãe e 106 Caiabi) e 33 mulheres em idade fértil. A pesquisa de marcadores sorológicos para HBV e HDV foi feita por técnica imunoenzimãtica. A prevalência global dos marcadores sorológicos nas crianças foi: HBsAg 4,5%; anti-HBs 39,6%; anti- HBc 44,1%; presença de algum marcador do HBV 47,3% e anti-HDV 0,0%, enquanto que nas mulheres em idade fértil foi: HBsAg 12%, todas anti-HBe positivas. A infecção pelo HBV ocoireu mais precocemente entre os Txucarramãe, quando se considerou algum marcador do HBV (p < 0,001). No PIX, área de alta endemicidadepara infecção pelo HBV, a transmissão do vírus ocorre provavelmente de maneira horizontal e não vertical como seria de se esperar, características culturais, condições de habitação e presença de insetos hematófagos são importantes determinantes na sua transmissão. Apesar de não ter sido detectado nenhum caso com hepatite Delta, o PIX é uma área propícia para a sua disseminação.

Tratamento da forma mucosa de leishmaniose sem resposta a glucantime, com anfotericina B liposomal

Tratamos com ambisome (2 a 5g totais de dose) seis pacientes com leishmaniose mucosa sem resposta a tratamento com glucantime (20mg SbV/kg/dia). A dose diária usada foi 2 a 3mg/kg/dia, aplicada por um mínimo de 20 dias. Após 26 a 38 meses de acompanhamento, cinco pacientes estão clinicamente curados. Um recidivou aos 6 meses. Não foram observados efeitos colaterais além de cefaléia, após a injeção. O ambisome constitue uma opção terapêutica para os pacientes com leishmaniose mucosa sem resposta aos antimoniais.

Prevalence of HIV-1/2, HTLV-I/II, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among prison inmates at Manhuaçu, Minas Gerais State, Brazil

The purpose of this study was to determine the seroprevalence of human immunodeficiency virus (HIV-1/2), human T-cell lymphotropic virus (HTLV-I/II), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum and Trypanosoma cruzi among 63 male prisoners in Manhuaçu, Minas Gerais, Brazil and to compare this with data from eligible blood donors. The positive results were as follows: 11/63 (17.5%) for HBV, 5/63 (7.4%) for syphilis, 4/63 (6.3%) for HCV, 3/63 (4.8%) for Chagas' disease, 2/63 (3.2%) for HIV-1/2 and 1/63 (1.6%) for HTLV-I/II. The seroprevalence in prisoners was higher than among blood donors, mainly for antibodies to HIV-1/2, HCV and HBV. This is probably due to low social economic level, illiteracy, higher proportion with a prior history of intravenous drug use and/or unsafe sexual behavior. Therefore, these prisoners constitute a high risk group and routine screening and counseling are recommended.

Prevalência de tripanossomíase americana, sífilis, toxoplasmose, rubéola, hepatite B, hepatite C e da infecção pelo vírus da imunodeficiência humana, avaliada por intermédio de testes sorológicos, em gestantes atendidas no período de 1996 a 1998 no Hospital Universitário Regional Norte do Paraná (Universidade Estadual de Londrina, Paraná, Brasil)

Com o objetivo de determinar a soroprevalência de tripanossomíase americana, sífilis, toxoplasmose, rubéola, hepatite B, hepatite C e infecção pelo vírus da imunodeficiência humana em gestantes atendidas no Hospital Universitário Regional Norte do Paraná, da Universidade Estadual de Londrina, Paraná, foi realizado estudo retrospectivo dos resultados dos testes sorológicos efetuados no período de junho de 1996 a junho de 1998. As taxas de positividade encontradas foram: 0,9% para tripanossomíase americana, 1,6% para sífilis, 67% (IgG) e 1,8% (IgM) para toxoplasmose, 89% (IgG) e 1,2% (IgM) para rubéola, 0,8% para hepatite B (AgHBs), 0,8% para hepatite C e 0,6% para infecção pelo vírus da imunodeficiência humana. Observou-se associação entre o aumento da soroprevalência de tripanossomíase americana com a idade das gestantes (p = 0,006). Os resultados reafirmam a importância da realização destes testes sorológicos no atendimento pré-natal, com a finalidade de realizar o diagnóstico e, eventualmente, adotar medidas para prevenir a transmissão congênita ou perinatal dessas doenças.