Riesgo de accidentes biológicos en estudiantes de la salud: revisión de la literatura en los últimos 14 años.

Introducción: Todos los trabajadores del área de la salud están en riesgo de padecer un accidente biológico. No obstante los estudiantes de estas aéreas, pueden presentar más riesgo porque apenas están en formación y no tienen la práctica o experiencia suficiente. Existen varios artículos que han estudiado la incidencia y prevalencia de accidentes biológicos en los trabajadores del área de la salud, Sin embargo, sobre esta problemática de la población estudiantil del área de la salud, se encuentra menos literatura. Por lo tanto con esta revisión sistemática se busca analizar y actualizar este tema. Métodos: Se realizó una revisión de la literatura científica de artículos publicados en los últimos 14 años, en relación con la prevalencia de accidentes biológicos en estudiantes de medicina, odontología, enfermería y residentes del área de la salud a nivel mundial. Se llevó a cabo la búsqueda en la base de datos de Pubmed, encontrando un total de 100 artículos, escritos en inglés, francés, español o portugués. Resultados: Las prevalencias encontradas sobre accidentes biológicos en estudiantes fueron las siguientes: en países europeos a nivel de enfermería los valores oscilan entre 10.2 % a 32%, en medicina fueron del 16%-58.8%, y en odontología del 21 %. En países asiáticos, se encontró que en enfermería el porcentaje varía de 49%-96 %, en medicina van del 35% -68%, y en odontología varia de 68.a 75.4%. En Norte América, en medicina las cifras fluctúan alrededor del 11-72.7 % y en odontología giran alrededor del 19.1%. Finalmente respecto a Suramérica la prevalencia fue de 31.2 a 46.7% en medicina, y del 40% en enfermería. Conclusiones: Por lo anterior se pudo concluir que, la prevalencia de accidentes biológicos en los estudiantes del área de la salud es elevada y varía según el continente en el que se encuentren.

Prevalence of hepatitis B and C serological markers among first-time blood donors in Brazil: A multi-center serosurvey

Little data are available on the seroprevalence of, and risk factors for hepatitis B and C viruses (HBV and HCV) infection in Latin American countries. A multi-center serosurvey was conducted among 3,598 first-time blood donors (65% men) from Sao Paulo, Salvador and Manaus in Brazil. The gender-specific seroprevalences of antibodies against hepatitis B core antigen (anti-HBc) and of the hepatitis B surface antigen (HBsAg) in anti-HBc-positive sera were measured, and risk factors analyzed by gender. The gender-specific seroprevalences of antibodies against HCV (anti-HCV) were measured, but risk factors for HCV were not determined. Anti-HBc and HBsAg seroprevalences were not significantly different in men [101/2,341 (4.31%) and 4/2,229 (0.18%), respectively] and women [65/1,237 (5.25%) and 8/ 1,169 (0.68%), respectively], whereas the seroprevalence of anti-HCV was higher in women (12/1,238 [0.97%] vs. 9/2,353 [0.38%]; odds ratio [OR] = 2.49; 95% confidence interval [Cl]: 1.0-6.0). No significant difference for HBV infection was found across the three study sites or by ethnic group. The seroprevalence of anti-HBc increased with age, but decreased with education level in both genders. Lifetime number of sexual partners was associated with anti-HBc prevalence among men (OR = 1.95; 95% Cl: 1.2-3.1), but not women. The seroprevalence of HBV and HCV was low among Brazilian blood donors, and exposure increased with age in both genders.

Avaliação da carga viral do virus da hepatite C em diferentes compartimentos biológicos: influência na predição da recidiva virológica

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Soroepidemiologia da infecção pelo Vírus da hepatite B (VHB) e pelo Vírus da hepatite C (VHC) em cirurgiões-dentistas da cidade de Belém, Pará

As hepatites virais representam um importante problema de saúde pública no Brasil e no mundo. A hepatite B e a hepatite C são as de principal interesse para os profissionais da área de saúde em função do modo de transmissão e da possibilidade de aquisição ocupacional. O presente trabalho teve por principal objetivo verificar a soroprevalência da infecção pelo Vírus da Hepatite B (VHB) e pelo Vírus da Hepatite C (VHC) em cirurgiões-dentistas e relacioná-la com os fatores de risco. Participaram do estudo 97 cirurgiões-dentistas, sendo 39 do gênero masculino e 58 do gênero feminino, no período de junho a dezembro de 2005, que atuam no município de Belém, Pará, Brasil. Os dados epidemiológicos foram obtidos por meio de inquéritos e os sorológicos por um ensaio imunoenzimático para a pesquisa de antígeno e anticorpo tanto para o VHB quanto para o VHC. O teste de Tendência foi utilizado para a análise estatística dos resultados. A prevalência do VHB foi de 6,2%, enquanto do VHC foi de 3,1% entre a população estudada. Das amostras sororreativas para os marcadores da hepatite B, a prevalência foi de 1,03% (1/97) para o anti-HBc total, 5,16% (5/97) para a presença simultânea do anti-HBc total e anti-HBs e 54,61% (53/97) para o anti-HBs. Quando comparado ao encontrado na população de doadores de sangue no Estado do Pará a prevalência do VHC na população estudada foi significativamente maior, enquanto a do VHB foi semelhante. Além disso, 37,7% (36/97) relataram terem tido algum tipo de exposição ocupacional, estando o acidente com objetos pérfuro-cortante como o mais relatado (86,1%). A medida adotada após a exposição foi sempre a lavagem com água e sabão e apenas 2,8% (1/36) dos acidentados relataram à realização de testes sorológicos. O conhecimento das normas de biossegurança e a utilização de pelo menos uma barreira de proteção individual foram relatados por todos, sendo o uso de luvas e máscara a resposta mais mencionada (96,9%). Encontravam-se imunizados contra o VHB por meio de vacina 54,61% (53/97) dos cirurgiões-dentistas, enquanto que imunes por infecção natural 5,16% (5/97). O elevado percentual de ocorrência de acidentes ocupacionais, aliado a baixa soroconversão pós-exposição dentre os cirurgiões-dentistas participantes demonstra a necessidade de se conhecer a prevalência de infecções de risco ocupacional em profissionais da área de saúde para que se adotem medidas de prevenção e controle mais eficazes contra os agentes causadores.

Molecular evolution of primate immunodeficiency viruses and hepatitis delta virus

Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous within an infected patient and among individuals. Substitution rates in the virus genomes are high and vary in different lineages and among sites. Methods of phylogenetic analysis were applied to study the evolution of primate lentiviruses and the hepatitis delta virus. The following results have been obtained: (1) The substitution rate varies among sites of primate lentivirus genes according to the two parameter gamma distribution, with the shape parameter $\alpha$ being close to 1. (2) Primate immunodeficiency viruses fall into species-specific lineages. Therefore, viral transmissions across primate species are not as frequent as suggested by previous authors. (3) Primate lentiviruses have acquired or lost their pathogenicity several times in the course of evolution. (4) Evidence was provided for multiple infections of a North American patient by distinct HIV-1 strains of the B subtype. (5) Computer simulations indicate that the probability of committing an error in testing HIV transmission depends on the number of virus sequences and their length, the divergence times among sequences, and the model of nucleotide substitution. (6) For future investigations of HIV-1 transmissions, using longer virus sequences and avoiding the use of distant outgroups is recommended. (7) Hepatitis delta virus strains are usually related according to the geographic region of isolation. (8) Evolution of HDV is characterized by the rate of synonymous substitution being lower than the nonsynonymous substitution rate and the rate of evolution of the noncoding region. (9) There is a strong preference for G and C nucleotides at the third codon positions of the HDV coding region. ^

Hepatitis B and C in Switzerland - healthcare provider initiated testing for chronic hepatitis B and C infection

Hepatitis B and hepatitis C are contagious liver diseases caused by the hepatitis B virus (HBV) and the hepatitis C virus (HCV), respectively. In particular, chronic infection with HBV or HCV is a major public health problem throughout Europe. The majority of persons chronically infected (65%-75%) are not aware of their infection status until symptoms of advanced liver disease appear. In addition, the peak in the number of patients suffering from advanced stages of the disease, such as cirrhosis and hepatocellular carcinoma, has not yet been reached. In order to reduce the current and future morbidity and mortality associated with chronic HBV or HCV infection, the timely detection of chronically infected persons, with follow-up and case management, is crucial. However, the current screening strategies in Europe and Switzerland have to be considered as inadequate to detect the majority of chronically infected persons. Hence, we emphasise the importance of an alternative approach: the healthcare provider initiated identification of HBV or HCV infection in defined risk groups. This entails determining whether a person is not only at risk of being chronically infected, but also at risk of becoming infected with HBV or HCV and, if necessary, testing for HBV or HCV infection.

Hepatitis B und C bei HIV-Koinfektion

Hepatitis B and C virus infections are a leading cause of death in HIV-positive patients. Furthermore, the management of these infections is complicated. Psychosocial problems and comorbidities are frequent barriers to the optimal management of these patients. Furthermore, the rapid changes in treatment strategies particularly in Hepatitis C make it difficult to treat patients outside specialized centers. An improvement in treatment uptake and efficacy can only be achieved through coordinated efforts between private care physicians and specialized centers.

Molecular epidemiology of hepatitis B virus infection in Switzerland: a retrospective cohort study.

BACKGROUND Chronic hepatitis B virus (HBV) infection affects up to 7 % of the European population. Specific HBV genotypes are associated with rapid progression to end-stage liver disease and sub-optimal interferon treatment responses. Although the geographic distribution of HBV genotypes differs between regions, it has not been studied in Switzerland, which lies at the crossroads of Europe. METHODS In a retrospective analysis of 465 HBV samples collected between 2002 and 2013, we evaluated the HBV genotype distribution and phylogenetic determinants, as well as the prevalence of serological evidence of hepatitis delta, hepatitis C and HIV infections in Switzerland. Baseline characteristics of patients were compared across their region of origin using Fisher's exact test and ANOVA, and risk factors for HBeAg positivity were assessed using logistic regression. RESULTS The Swiss native population represented 15.7 % of HBV-infected patients living in Switzerland. In the overall population, genotype D was most prevalent (58.3 %), whereas genotype A (58.9 %) was the predominant genotype among the Swiss native population. The prevalence of patients with anti-HDV antibodies was 4.4 %. Patients of Swiss origin were most likely to be HBeAg-positive (38.1 %). HBV genotypes of patients living in Switzerland but sharing the same original region of origin were consistent with their place of birth. CONCLUSIONS The molecular epidemiology of HBV infection in Switzerland is driven by migration patterns and not by the genotype distribution of the native population. The prevalence of positive anti-HDV antibodies in our cohort was very low.

Hepatitis B and C infections in U.S. incarcerated populations: Prevalence and related mortality

Published reports have consistently indicated high prevalence of serologic markers for hepatitis B (HBV) and hepatitis C (HCV) infection in U.S. incarcerated populations. Quantifying the current and projected burden of HBV and HCV infection and hepatitis-related sequelae in correctional healthcare systems with even modest precision remains elusive, however, because the prevalence and sequelae of HBV and HCV in U.S. incarcerated populations are not well-studied. This dissertation contributes to the assessment of the burden of HBV and HCV infections in U.S. incarcerated populations by addressing some of the deficiencies and gaps in previous research. ^ Objectives of the three dissertation studies were: (1) To investigate selected study-level factors as potential sources of heterogeneity in published HBV seroprevalence estimates in U.S. adult incarcerated populations (1975-2005), using meta-regression techniques; (2) To quantify the potential influence of suboptimal sensitivity of screening tests for antibodies to hepatitis C virus (anti-HCV) on previously reported anti-HCV prevalence estimates in U.S. incarcerated populations (1990-2005), by comparing these estimates to error-adjusted anti-HCV prevalence estimates in these populations; (3) To estimate death rates due to HBV, HCV, chronic liver disease (CLD/cirrhosis), and liver cancer from 1984 through 2003 in male prisoners in custody of the Texas Department of Criminal Justice (TDCJ) and to quantify the proportion of CLD/cirrhosis and liver cancer prisoner deaths attributable to HBV and/or HCV. ^ Results were as follows. Although meta-regression analyses were limited by the small body of literature, mean population age and serum collection year appeared to be sources of heterogeneity, respectively, in prevalence estimates of antibodies to HBV antigen (HBsAg+) and any positive HBV marker. Other population characteristics and study methods could not be ruled out as sources of heterogeneity. Anti-HCV prevalence is likely somewhat higher in male and female U.S. incarcerated populations than previously estimated in studies using anti-HCV screening tests alone without the benefit of repeat or additional testing. Death rates due to HBV, HCV, CLD/cirrhosis, and liver cancer from 1984 through 2003 in TDCJ male prisoners exceeded state and national rates. HCV rates appeared to be increasing and disproportionately affecting Hispanics. HCV was implicated in nearly one-third of liver cancer deaths. ^

Determinación de la actividad de la óxido nítrico sintetasa endotelial y del factor NF-kB, en la piel del paciente con pseudoangiomatosis eruptiva : informe preliminar

La pseudoangiomatosis eruptiva se caracteriza por la aparición brusca de múltiples pápulas eritematosas, asintomáticas, rodeadas de un halo blanquecino, con remisión espontánea. Histológicamente se observa dilatación vascular con escaso infiltrado inflamatorio. Su etiología permanece incierta a pesar de ser relacionada con virus o picaduras de insectos. Basados en el compromiso vascular, el objetivo del trabajo fue investigar la actividad de la enzima endotelial oxido nítrico sintetasa (eNOS) y la expresión del factor NF-kB por inmunohistoquimica en un intento de esclarecer su patogenia. Material y métodos: Se estudiaron diez pacientes con diagnóstico clínico de pseudoangiomatosis eruptiva (PAE) que presentaron la dermatosis en forma epidémica. Se realizaron biopsias teñidas con Hematoxilina-Eosina y Tricrómico de Masson. Se efectuó estudio virológico de los pacientes Nª 4, 9 y 10 mediante determinaciones serológicas para echovirus, enterovirus, citomegalovirus, parvovirus B19 y hepatitis A, B y C. En cinco pacientes se obtuvo material para determinación de eNOS y NF-kB. Resultados: Todos los pacientes, 5 hombres y 5 mujeres presentaron pápulas eritematosas rodeadas por un halo blanquecino, especialmente en las extremidades, alrededor de las rodillas. Histológicamente mostraron vasos dilatados y células endoteliales prominentes con un infiltrado discreto perivascular. Todos los estudios serológicos fueron negativos. La actividad de eNOS fue significativamente menor comparada con la piel normal (p= 0,002) y la expresión de NF- ĸB fue fuertemente positiva en los vasos de la dermis papilar y reticular. Conclusiones: Todos los pacientes fueron afectados en verano, por lo que la picadura del mosquito debe ser considerada como un factor etiológico. La baja expresión de eNOS está relacionada con la vasodilatación y la expresión aumentada de NF-ĸB confirma que el proceso es de tipo inflamatorio.

The nuclear pore complex and its transporters : from virus-host interactors to subverting the innate antiviral immunity

Les virus ont besoin d’interagir avec des facteurs cellulaires pour se répliquer et se propager dans les cellules d’hôtes. Une étude de l'interactome des protéines du virus d'hépatite C (VHC) par Germain et al. (2014) a permis d'élucider de nouvelles interactions virus-hôte. L'étude a également démontré que la majorité des facteurs de l'hôte n'avaient pas d'effet sur la réplication du virus. Ces travaux suggèrent que la majorité des protéines ont un rôle dans d'autres processus cellulaires tel que la réponse innée antivirale et ciblées pas le virus dans des mécanismes d'évasion immune. Pour tester cette hypothèse, 132 interactant virus-hôtes ont été sélectionnés et évalués par silençage génique dans un criblage d'ARNi sur la production interferon-beta (IFNB1). Nous avons ainsi observé que les réductions de l'expression de 53 interactants virus-hôte modulent la réponse antivirale innée. Une étude dans les termes de gène d'ontologie (GO) démontre un enrichissement de ces protéines au transport nucléocytoplasmique et au complexe du pore nucléaire. De plus, les gènes associés avec ces termes (CSE1L, KPNB1, RAN, TNPO1 et XPO1) ont été caractérisé comme des interactant de la protéine NS3/4A par Germain et al. (2014), et comme des régulateurs positives de la réponse innée antivirale. Comme le VHC se réplique dans le cytoplasme, nous proposons que ces interactions à des protéines associées avec le noyau confèrent un avantage de réplication et bénéficient au virus en interférant avec des processus cellulaire tel que la réponse innée. Cette réponse innée antivirale requiert la translocation nucléaire des facteurs transcriptionnelles IRF3 et NF-κB p65 pour la production des IFNs de type I. Un essai de microscopie a été développé afin d'évaluer l’effet du silençage de 60 gènes exprimant des protéines associés au complexe du pore nucléaire et au transport nucléocytoplasmique sur la translocation d’IRF3 et NF-κB p65 par un criblage ARNi lors d’une cinétique d'infection virale. En conclusion, l’étude démontre qu’il y a plusieurs protéines qui sont impliqués dans le transport de ces facteurs transcriptionnelles pendant une infection virale et peut affecter la production IFNB1 à différents niveaux de la réponse d'immunité antivirale. L'étude aussi suggère que l'effet de ces facteurs de transport sur la réponse innée est peut être un mécanisme d'évasion par des virus comme VHC.

Caractérisation des inhibiteurs de DCIR, une lectine de type C participant à la transmission du VIH-1

Le virus de l’immunodéficience humaine de type 1 provoque une infection définitive de l’organisme. Il entraine une déroute du système immunitaire depuis la primo-infection occasionnant ainsi, une déplétion massive des lymphocytes T CD4 (LTCD4). Le DCIR (Dendritic Cell Immuno Receptor) qui constitue le socle de notre travail, est une lectine de type C. Il est exprimé sur les cellules myéloïdes comme les cellules dendritiques mais aussi sur les cellules B, les LTCD4 infectés par le VIH-1 et apoptotiques ainsi que sur les LTCD4 polarisés en Th17. Il constitue un facteur d’attachement et d’internalisation du virus dans la cellule dendritique. Il permet son transfert aux LTCD4 dans les organes lymphoïdes secondaires, jouant ainsi un rôle dans la pathogenèse associée au VIH-1. En plus, le DCIR assure la régulation négative de la réponse cellulaire, favorisant ainsi la propagation et la réplication du virus au détriment de la réponse immunitaire contre le VIH-1. Le rôle que joue le DCIR est dépendant du sentier de signalisation induit à la suite de la phosphorylation des résidus tyrosine de son motif ITIM. Le blocage de DCIR par des inhibiteurs spécifiques pourrait empêcher cette phosphorylation et réduire l’attachement, l’internalisation et le transfert du virus. Nous avons montré que la stimulation des cellules dendritiques et des LTCD4 polarisés en Th17 avec un anticorps anti-DCIR générait un patron de phosphorylation des résidus tyrosine des protéines. De plus, les inhibiteurs de la portion extracellulaire du DCIR inhibent cette activation. Afin de développer une mesure plus directe de l’interaction de DCIR avec ces inhibiteurs, nous avons purifié le DCIR à partir des cellules Raji-CD4-DCIR. En conclusion, ce projet de maitrise montre que l’activation directe de DCIR peut être renversée par des inhibiteurs montrant ainsi leurs spécificités. De plus, le profil d’activation de DCIR est spécifique pour chaque type cellulaire. A long terme, l’inactivation de DCIR par des inhibiteurs efficaces pourrait être une stratégie thérapeutique capable d’inhiber l’infection et de préserver une réponse immunitaire efficace.

Hepatitis B and C prevalence in Portugal: disparity between the general population and high-risk groups

Background and aims: The prevalence of anti-HCV and HBsAg in Portugal has been shown to be elevated in high-risk groups, such as intravenous drug-users and incarcerated individuals. However, in the general population, prevalence remains largely unknown. The aims of this study were to estimate the prevalence of anti-HCV and HBsAg in the general Portuguese population and identify associated risk factors. Materials and methods: We carried out a nationwide, population-based cross-sectional study of adults resident in mainland Portugal. Serology for HBsAg, anti-HBc, anti-HBs, and anti-HCV was performed. Anti-HCV-positive individuals were tested for HCV RNA by PCR. Results: Of 1685 participants, 50.6% were men, mean age 50.2±18.3 years. In terms of hepatitis C, the prevalence of anti-HCV was 0.54% [95% confidence interval (CI): 0.2–0.9] and 0.12% (95% CI: 0.0–0.3) were viremic, with peak prevalence among individuals 35–64 years of age (0.8%), men (0.8%), and individuals from Lisbon and Tagus Valley region (1.9%). In terms of hepatitis B, the estimated prevalence of HBsAg was 1.45% (95% CI: 0.9–2.0). A higher prevalence was found in individuals who were 35–64 years old (2.2%), in men (2.5%), and in the Northern region (2.6%). The presence of positive serological markers of hepatitis C virus and hepatitis B virus infection did not correlate with elevated aminotransferases, race, place of birth, and alcohol consumption. Conclusion: These results suggest a low endemicity for both hepatitis B and hepatitis C in the general population, in contrast to a very high prevalence in risk groups, thus suggesting that targeted screening to high-risk groups may be more cost-effective than general population screening.

An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy.

Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients

Human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and -2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co-infected subjects may be at increased risk for tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)-like. To study the prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) among coinfected HIV-1/HTLV-1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV-1-infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases ""Emilio Ribas,"" in Sao Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. Results: A total of 38 HIV-1/HTLV-1 co-infected subjects were identified in this cohort: Twenty-six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co-infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow-up. No modifications on HIV-1 viral load was seen. In contrast, the co-infected with TSP/HAM-like group showed higher HTLV-1 proviral load (505 +/- 380 vs. 97 +/- 149 copies/10(4) PBMC, P= 0.012) than asymptomatic co-infected subjects, respectively. The incidence of myelopathy among HIV-1/HTLV-1 co-infected subjects is probably higher than among patients infected only with HTLV-1, and related to a higher HTLV-1 proviral load. Thus, HTLV-1/2 screening should be done for all HIV-1-infected patients in areas where HTLV-1 infection is endemic.