Detecção do vírus Epstein-Barr em tonsilites recorrentes

As tonsilites recorrentes têm sido objeto de muitos estudos. Eventos considerados na predisposição e causa incluem a utilização errônea de antibióticos em crises agudas, alterações da microflora, mudanças estruturais nas criptas epiteliais tonsilares e infecções virais. A infecção pelo vírus Epstein-Barr (EBV) ocorre freqüentemente na infância persistindo em linfócitos de tonsilas, podendo causar tonsilites recorrentes. Pouco se conhece sobre a persistência e reativação do EBV em pacientes imunocompetentes. Alguns métodos como a hibridização in situ, a reação em cadeia da polimerase (PCR) e a imuno-histoquímica têm sido utilizados no estudo da patogenia do vírus. OBJETIVO: Para caracterizar a associação do vírus Epstein-Barr com tonsilites recorrentes examinamos a presença do EBV pela PCR e por imuno-histoquímica usando como alvo a proteína viral LMP-1. FORMA DE ESTUDO: Estudo transversal com análise de prevalência amostral. MATERIAL E MÉTODOS: Foram selecionados 24 blocos parafinados de tonsilas, provenientes do Serviço de Anatomia Patológica, removidas de crianças de 2 a 12 anos com diagnóstico de tonsilite recorrente. Resultados: O genoma do EBV foi detectado em 13 (54,1%) e a LMP-1 em 9 (37,5%) dos casos. CONCLUSÃO: As tonsilas das crianças podem ser colonizadas pelo EBV e este pode estar associado à patogenia das tonsilites recorrentes.

Infection and childhood leukemia: review of evidence

OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection), and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

Implicações imunobiológicas da infecção a herpesvirus em tumores malignos : pesquisa e análise quantitativa de herpesvirus humanos no astrocitoma pilocítico

RESUMO: As infecções virais podem contribuir para o desenvolvimento do cancro, estando vários tumores malignos associados aos Herpesvirus (HHV). O vírus de Epstein-Barr (EBV) e o Herpesvirus 8, dois Herpesvirus, foram reconhecidos como agentes etiológicos de várias neoplasias. O astrocitoma pilocítico do cerebelo é um dos tumores cerebrais mais frequentes na criança, adolescentes e jovens adultos e a proliferação astrocitária ocorre geralmente após vários tipos de agressão, nomeadamente a infecção viral. Para investigar esta eventual interligação, estudámos 35 astrocitomas pilocíticos, pesquisando a presença dos 8 Herpesvirus. Neste estudo, foram utilizadas 10 amostras de biópsias do cerebelo de doentes que faleceram por doenças não relacionadas com infecção ou patologia tumoral. A maioria dos astrocitomas (33) eram tumores de baixa malignidade. As amostras foram analisadas por PCR (Polymerase Chain Reaction) quantitativa em tempo real (qPCR), com amplificação do gene da DNA polimerase viral. Treze astrocitomas e 7 controles revelaram pequenas quantidades de DNA viral (1-100 cópias/100ng DNA) de todos os Herpesvirus, com excepção do HHV6 A e B que estava ausente nas amostras. O EBV foi identificado em 9 dos 35 astrocitomas (26%) e em 7 dos 10 controles (70%) estando muito mais presente nos controles. As amostras positivas para o EBV foram também analisadas por imunohistoquímica, não tendo sido imunoreactivas para os anticorpos utilizados. A PCR com CODEHOP (consensus-degenerated hybrid oligonucleotide primers) foi utilizada para investigar a presença de um eventual Herpesvirus novo nestas amostras. Não foi identificada nenhuma sequência indicativa de um novo HHV por este método. 24. Em conclusão, os dados apontam para a presença de Herpesvirus, com particular relevância para o EBV, em tecido de cerebelo normal e em tumores cerebrais, embora em níveis demasiado baixos para poderem ser responsabilizados pela indução tumoral. A presença de sequências de DNA de Herpesvirus, nomeadamente do EBV, no Sistema Nervoso Central vem enriquecer a discussão sobre o significado da infecção viral na oncogénese humana, particularmente na neuro-oncogénese. ABSTRACT: Viral infections can contribute to the development of human cancer. Several human malignancies are linked with Human Herpesviruses (HHVs). Epstein-Barr virus and HHV8, two hHerpesvirus, have been recognized as etiologic agents of several neoplasms. Pilocytic astrocytoma of the cerebellum is one of the most common brain tumour in children, adolescents and young adults and astrocytary proliferation generally occurs after several types of injury, namely viral infection. To further explore this association, we have searched the tissue from 35 pilocytic astrocytoma, for all the 8 HHV. In this study, ten brain biopsies (cerebellum) from patients who died of unrelated diseases were used as controls. Most of the astrocytomas (33) were of low grade malignity. Samples were assessed by Real-time quantitative Polymerase Chain Reaction (q PCR) amplification of viral DNA polymerase gene. Thirteen astrocytoma and 7 controls showed low viral DNA levels (1-100 copies/100ng DNA) for all HHVs, with the exception of HHV6 that was absent. EBV was identified in 9 of the 35 astrocytoma (26 %) and in 7 of the 10 controls (70%) being more present in controls. EBV positive samples were also assessed by Immunohistochemistry (IHC) but none showed immunoreactivity for the antibodies used. PCR with consensus-degenerated hybrid oligonucleotide primers (CODEHOP) were also used to look for novel HHVs in these samples and no sequence indicative of a new HHV was detected. 26 Altogether the data indicate the presence of HHVs, with relevance for EBV in normal cerebellum tissue and also in brain tumours but at too low levels to be considered responsible for tumour induction. The presence of HHV DNA sequences, particularly EBV, in the studied brain tumours and control samples, further enriches the discussion about the relevance of viral infection in human oncogenesis, particularly neuro-oncogenesis.RÉSUMÉ: Les infections virales peuvent contribuer au développement du cancer. Les vírus de type Herpès sont associés à plusieurs néoplasies. Il est par exemple établi que les vírus Epstein-Barr et « human Herpesvirus 8 » (HHV-8) sont responsables de plusieurs tumeurs malignes. L´astrocytome pilocitique du cervelet est l’une des tumeurs les plus fréquentes chez les enfants, adolescents et adultes jeunes. En général la prolifération des astrocytes se produit en réponse à une agression. Posant l’hypothèse d’une agression d’origine virale, nous avons recherché la présence des 8 vírus Herpès dans les tissus de 35 astrocytomes. Dans cette étude, 10 échantillons de biopsie de cervelet de patients décédés suite à d’autres pathologies, ont été utilisés comme contrôles. La majorité des astrocytomes étaient de très basse malignité. Les échantillons ont été étudiés par PCR quantitative en temps réel, en amplifiant le gène de l’ADN-polymérase virale. Treize astrocytomes sur 35 (37%) et 7 contrôles sur 10 (70%) ont été trouvés positifs pour tous les HHV sauf l´HHV6, toujours avec un nombre de copies de polymérase virale bas (< 100 copies/100 ng d’ADN). Notamment l’EBV a été identifié 7 fois dans les contrôles (70%) et 9 fois dans les astrocytomes (26%). Les échantillons positifs pour l`EBV ont aussi été étudiés par immuno-histochimie. Aucun signal n’a été observé avec les anticorps utilisés. Enfin, une technique de PCR avec oligonucléotides dégénérés (CODEHOP ou consensus degenerated hybrid oligonucleotide primers) a été utilisée pour rechercher la présence d´un éventuel nouveau vírus Herpès dans les échantillons d’astrocytome. Aucun nouveau vírus n’a été identifié. 28 En résumé, nous avons établi la présence de vírus Herpès, en particulier l´EBV, dans le cervelet normal et dans les tumeurs du cerveau. Les quantités d’ADN viral retrouvées sont faibles et ne permettent pas d’attribuer à ces vírus la responsabilité de l’induction des tumeurs. Cependant, la présence d’ADN de vírus Herpès dans le cerveau sain ou pathologique vient enrichir la discussion sur le signification de l´infection virale dans les processus d´oncogenèse en général, et dans la neuroonco-genèse en particulier.

Chronic hepatitis C virus infections in Brazilian patients: association with genotypes, clinical parameters and response to long term alpha interferon therapy

The present study assessed the clinical significance of hepatitis C virus (HCV) genotypes and their influence on response to long term recombinant-interferon-alpha (r-IFN-a) therapy in Brazilian patients. One hundred and thirty samples from patients previously genotyped for the HCV and with histologically confirmed chronic hepatitis C (CH-C) were evaluated for clinical and epidemiological parameters (sex, age, time of HCV infection and transmission routes). No difference in disease activity, sex, age or mode and time of transmission were seen among patients infected with HCV types 1, 2 or 3. One hundred and thirteen of them were treated with 3 million units of r-IFN-a, 3 times a week for 12 months. Initial response (IR) was significantly better in patients with genotype 2 (100%) and 3 (46%) infections than in patients with genotype 1 (29%) (p < 0.005). Among subtypes, difference in IR was observed between 1b and 2 (p < 0.005), and between 1b and 3a (p < 0.05). Sustained response (SR) was observed in 12% for (sub)type 1a, 13% for 1b, 19% for 3a, and 40% for type 2; significant differences were found between 1b and 2 (p < 0.001), and between 1b and 3a (p < 0.05). Moreover, presence of cirrhosis was significantly associated with non response and response with relapse (p < 0.05). In conclusion, non-1 HCV genotype and lack of histological diagnosis of cirrhosis were the only baseline features associated with sustained response to treatment. These data indicate that HCV genotyping may have prognostic relevance in the responsiveness to r-IFN-a therapy in Brazilian patients with chronic HCV infection, as seen in other reports worldwide.

Current status of herpesvirus identification in the oral cavity of HIV-infected children

INTRODUCTION: Some viruses of the Herpesviridae family are frequently the etiologic agents of oral lesions associated with HIV. The aim of this study was to identify the presence of herpes simplex virus types 1 and 2 (HSV-1, HSV-2), Varicella Zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus type 6, type 7 and type 8 (HHV-6, HHV-7 and HHV-8) in the oral cavity of HIV-infected children/adolescents and verify the association between viral subtypes and clinical factors. METHODS: The cells of oral mucosa were collected from 50 HIV infected children/adolescents, 3-13 years old (mean age 8.66). The majority (66%) of selected were girls, and they were all outpatients at the pediatric AIDS clinic of a public hospital in Rio de Janeiro. Nested-PCR was used to identify the viral types. RESULTS: Absence of immunosuppression was observed in 66% of the children. Highly active antiretroviral therapy (HAART) was used by 72.1% of selected and moderate viral load was observed in 56% of the children/adolescents. Viral types were found in 86% of the children and the subtypes were: HSV-1 (4%), HSV-2 (2%), VZV (4%), EBV (0%), HCMV (24%), HHV6 (18%), HHV-7 (68%), HHV8 (0%). CONCLUSIONS: The use of HAART has helped to reduce oral lesions, especially with herpes virus infections. The health professionals who work with these patients should be aware of such lesions because of their predictive value and the herpes virus can be found circulating in the oral cavity without causing lesions.

Prevention of respiratory syncytial virus infections

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

Thymoma, immunodeficiency, and herpes simplex virus infections.

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

Effect of vitamin D on Epstein-Barr (EBV)-specific CD8+T cells in patients with early multiple sclerosis (MS)

Background: Infection with EBV and a lack in vitamin D may be important environmental triggers of MS. 1,25-(OH)2D3 mediates a shift of antigen presenting cells (APC) and CD4+ T cells to a less inflammatory profile. Although CD8+ T cells do express the vitamin D receptor, a direct effect of 1,25(OH)2D3 on these cells has not been demonstrated until now. Since CD8+ T cells are important immune mediators of the inflammatory response in MS, we examined whether vitamin D directly affects the CD8+ T cell response, and more specifically if it modulates the EBV-specific CD8+ T cell response. Material and Methods: To explore whether the vitamin D status may influence the pattern of the EBV-specific CD8+ T cell response, PBMC of 10 patients with early MS and 10 healthy controls (HC) were stimulated with a pool of immunodominant 8-10 mer peptide epitopes known to elicit CD8+ T cell responses. PBMC were stimulated with this EBV CD8 peptide pool, medium (negative control) or anti- CD3/anti-CD28 beads (positive control). The following assays were performed: ELISPOT to assess the secretion of IFN-gamma by T cells in general; cytometric beads array (CBA) and ELISA to determine whichcytokines were released by EBV-specific CD8+ T cells after six days of culture; and intracellular cytokine staining assay to determine by which subtype of T cells secreted given cytokines. To examine whether vitamin D could directly modulate CD8+ T cell immune responses, we depleted CD4+ T cells using negative selection. Results: We found that pre-treatment of vitamin D had an antiinflammatory action on both EBV-specific CD8+ T cells and on CD3/ CD28-stimulated T cells: secretion of pro-inflammatory cytokines (IFNgamma and TNF-alpha) was decreased, whereas secretion of antiinflammatory cytokines (IL-5 and TGF-beta) was increased. At baseline, CD8+ T cells of early MS patients showed a higher secretion of TNFalpha and lower secretion of IL-5. Addition of vitamin D did not restore the same levels of both cytokines as compared to HC. Vitamin D-pretreated CD8+T cells exhibited a decreased secretion of IFN-gamma and TNF-alpha, even after depletion of CD4+ T cells from culture. Conclusion: Vitamin D has a direct anti-inflammatory effect on CD8+ T cells independently from CD4+ T cells. CD8+ T cells of patients with earlyMS are less responsive to the inflammatory effect of vitamin D than HC, pointing toward an intrinsic dysregulation of CD8+ T cells. The modulation of EBV-specific CD8+T cells by vitaminDsuggests that there may be interplay between these twomajor environmental factors of MS. This study was supported by a grant from the Swiss National Foundation (PP00P3-124893), and by an unrestricted research grant from Bayer to RDP.

Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression.

Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed of CD127(+) perforin(-)/CD127(-) perforin(+), and CD127(-)/perforin(-) CD8 T cells, respectively. CD127(-)/perforin(-) and CD127(-)/perforin(+) cells expressed significantly more PD-1 and CD57, respectively. Consistently, intracellular cytokine (gamma interferon, tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to perforin detection confirmed that virus-specific CD8 T cells were mostly composed of either perforin(+)/IL-2(-) or perforin(-)/IL-2(+) cells. In addition, perforin expression and IL-2 secretion were negatively correlated in virus-specific CD8 T cells (P &lt; 0.01). As previously shown for perforin, changes in antigen exposure modulated also CD127 expression. Based on the above results, proliferating (CD127(+)/IL-2-secreting) and cytotoxic (perforin(+)) CD8 T cells were contained within phenotypically distinct T-cell populations at different stages of activation or differentiation and showed different levels of exhaustion and senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T cells for a given antiviral CD8 T-cell population appeared to be influenced by antigen exposure. These results advance our understanding of the relationship between cytotoxicity, proliferation capacity, the levels of senescence and exhaustion, and antigen exposure of antiviral memory CD8 T cells.

Respiratory syncytial virus infections during an epidemic period in Salvador, Brazil: viral antigenic group analysis and description of clinical and epidemiological aspects

Acute respiratory infections (ARI) caused by respiratory syncytial virus (RSV) were studied in 482 children from Salvador, BA, Brazil, over a period of 12 months. The epidemic period of RSV infections in Salvador occurred from February (summer) to August (winter), with peaks in May, June, and July. The grouping characteristics of 84 RSV present in nasopharyngeal secretions of children seen at a reference university hospital were analyzed. RSV represented 17.4% of all cases and 54.5% of the positive samples. Sixty-four RSV strains were assigned to group A and 14 to group B. Both groups circulated in the five months of the epidemic period studied. Infections by both groups of RSV were more frequent in children up to one year of age. The incidence of RSV ARI was slightly more frequent in males, although group B had more infected females.

Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and implication for NF-Κb activation.

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.

Primary dengue virus infections induce differential cytokine production in Mexican patients

Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient’s clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcription-polymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.

Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study.

BACKGROUND: Natalizumab is used to prevent relapses and progression of disability in patients with multiple sclerosis but has been associated with progressive multifocal leukoencephalopathy (PML). We aimed to better understand the associations between JC virus, which causes PML, and natalizumab treatment. METHODS: We prospectively assessed patients with multiple sclerosis who started treatment with natalizumab. Blood and urine samples were tested for the presence of JC virus DNA with quantitative real-time PCR before treatment and at regular intervals after treatment onset for up to 18 months. At the same timepoints, by use of proliferation and enzyme-linked immunospot assays, the cellular immune responses against JC virus, Epstein-Barr virus, cytomegalovirus, myelin oligodendrocyte glycoprotein, and myelin oligodendrocyte basic protein (MOBP) were assessed. Humoral immune response specific to JC virus was assessed with an enzyme immunoassay. The same experiments were done on blood samples from patients with multiple sclerosis before and 10 months after the start of interferon beta treatment. FINDINGS: We assessed 24 patients with multiple sclerosis who received natalizumab and 16 who received interferon beta. In patients treated with natalizumab, JC virus DNA was not detected in the blood at any timepoint. However, JC virus DNA was present in the urine of six patients and in most of these patients the concentrations of JC virus DNA were stable over time. Compared with pretreatment values, the cellular immune response was increased to cytomegalovirus at 6 months, to JC virus at 1, 9, and 12 months, and to Epstein-Barr virus and MOBP at 12 months. Humoral responses remained stable. There were no increases in cellular immune responses specific to the viruses or myelin proteins in the 16 patients treated with interferon beta. INTERPRETATION: Natalizumab increases cellular immune responses specific to viruses and myelin proteins in the peripheral blood after 1 year, without evidence of viral reactivation. FUNDING: Swiss National Foundation, Swiss Society for Multiple Sclerosis, and Biogen Dompé.

Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic.

BACKGROUND: Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS). METHODS: HCV infection incidence was assessed from 1998, when routine serial HCV screening was introduced in the SHCS, until 2011. All HCV-seronegative patients with at least 1 follow-up serology were included. Incidence rates (IRs) of HCV infections were compared between men who have sex with men (MSM), injection drug users (IDU), and heterosexuals (HET). RESULTS: HCV incidence was assessed in 3333 MSM, 123 IDU, and 3078 HET with a negative HCV serology at baseline. Over 23 707 person-years (py) for MSM, 733 py for IDU, and 20 752 py for HET, 101 (3%), 41 (33%), and 25 (1%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained <1 per 100 py in HET. In MSM, history of inconsistent condom use (adjusted hazard ratio [HR], 2.09; 95% CI, 1.33-3.29) and past syphilis (adjusted HR, 2.11; 95% confidence interval [CI], 1.39-3.20) predicted HCV seroconversion. CONCLUSIONS: In the SHCS, HCV infection incidence decreased in IDU, remained stable in HET, and increased 18-fold in MSM in the last 13 years. These observations underscore the need for improved HCV surveillance and prevention among HIV-infected MSM.

Decrease in the prevalence of hepatitis B and a low prevalence of hepatitis C virus infections in the general population of the Seychelles.

A serological survey of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was carried out on a random sex- and age-stratified sample of 1006 individuals aged 25-64 years in the Seychelles islands. Anti-HBc and anti-HCV antibodies were detected using commercially available enzyme-linked immunosorbent assays (ELISA), followed by a Western blot assay in the case of a positive result for anti-HCV. The age-adjusted seroprevalence of anti-HBc antibodies was 8.0% (95% CI: 6.5-9.9%) and the percentage prevalence among males/females increased from 7.0/3.1 to 19.1/13.4 in the age groups 25-34 to 55-64 years, respectively. Two men and three women were positive for anti-HCV antibodies, with an age-adjusted seroprevalence of 0.34% (95% CI: 0.1-0.8%). Two out of these five subjects who were positive for anti-HCV also had anti-HBc antibodies. The seroprevalence of anti-HBc was significantly higher in unskilled workers, persons with low education, and heavy drinkers. The age-specific seroprevalence of anti-HBc in this population-based survey, which was conducted in 1994, was approximately three times lower than in a previous patient-based survey carried out in 1979. Although there are methodological differences between the two surveys, it is likely that the substantial decrease in anti-HBc prevalence during the last 15 years may be due to significant socioeconomic development and the systematic screening of blood donors since 1981. Because hepatitis C virus infections are serious and the cost of treatment is high, the fact that the prevalence of anti-HCV antibodies is at present low should not be an argument for not screening blood donors for anti-HCV and eliminating those who are positive.