Recurrent hepatitis C treatment with direct acting antivirals : a real life study at a brazilian liver transplant center

Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2–228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2–16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied52

Clinical, epidemiological, and microbiological characteristics of bacteremia caused by high-level gentamicin-resistant Enterococcus faecalis

Enterococcus spp bacteremia is associated with high mortality and the appearance of high-level gentamicin resistance (HLGR) created additional challenges for the treatment of these infections. We evaluated the epidemiological and clinical characteristics of patients with bacteremias caused by HLGR and non_HLGR Enterococcus faecalis isolates at a teaching hospital in the State of São Paulo, Brazil. Patients with bacteremia due to E. faecalis diagnosed between January 1999 and December 2003 were included in the study. We collected clinical, epidemiological, and microbiological data from medical records. Banked isolates were typed using pulsed-field gel electrophoresis. We identified 145 cases of E. faecalis bacteremia: 66 (45.5%) were caused by HLGR isolates and 79 (54.5%) by non_HLGR. In the univariate analysis, patients with HLGR infection were older, had higher rates of bladder catheterization, and more often had treatment with cephalosporin, quinolone, and/or carbapenem compared with patients with non_HLGR infection (P < 0.05). Multivariate analysis indicated that older age, hematological malignancy, and previous use of vancomycin were independently associated with HLGR (P < 0.05). Mortality rates were not significantly different among patients with HLGR (50%) and non_HLGR (43%) infections (P = 0.40). Of the 32 genotyped isolates, 16 were distributed into 6 main electrophoresis patterns and 16 others had distinct patterns. E. faecalis bacteremia is associated with high mortality and is frequently caused by HLGR isolates at this teaching hospital. The variability among genotyped isolates suggests that endogenous infections, rather than patient-to-patient transmission of E. faecalis, are more common at this institution.89089

A Clinical, Epidemiological, Laboratorial, Histological And Ultrasonographical Evaluation Of Anti-hcv Eia-2 Positive Blood Donors

Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83.5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathologieal exams of the anti-HCV EIA-2 reagent donors which were, indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.423147152Alter, H.J., To C or not to C: These are the questions (1995) Blood, 85, pp. 1631-1695Alter, H.J., Conry-Cantilena, C., Melpolder, J., Hepatitis C in asymptomatic blood donors (1997) Hepatology, 26 (1 SUPPL.), pp. 29S-33SAlter, H.J., Purcell, R.H., Shih, J.W., Detection of antibodies to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis (1989) New Engl. J. Med., 321, pp. 1494-1500Alter, H.J., Tegtmeier, G., Jett, B., The use of a recombinant immunoblot assay in the interpretation of anti-hepatitis C virus reactivity among prospectively followed patients, implicated donors, and random donors (1991) Transfusion, 31, pp. 771-776Alter, M.J., Epidemiology of hepatitis C in the West (1995) Semin. Liver Dis., 15, pp. 5-14Areias, J., Pedroto, I., Freitas, T., Hepatitis C virus carriers with normal ALT activity: Viraemia, genotype and effect of interferon therapy (1996) Gastroenterology, 110, pp. A1143Choo, Q.L., Kuo, G., Weiner, A.J., Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome (1989) Science, 244, pp. 359-362Conry-Cantilena, C., Van Raden, M., Gibble, J., Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C infection (1996) New Engl. J. Med., 334, pp. 1691-1696Esteban, J.I., Esteban, R., Viladomiu, L., Hepatitis C virus antibodies among risk groups in Spain (1989) Lancet, 2, pp. 294-297Esteban, J.I., Gonzales, A., Hernandez, J.M., Evaluation of antibodies to hepatitis C virus in a contemporary study of transfusion-associated hepatitis (1990) New Engl. J. Med., 323, pp. 1107-1112Garcia-Samaniego, J., Enriquez, A., Soriano, V., Third-generation recombinant immunoblot assay to confirm hepatitis C virus-indeterminate serological samples (1993) Vox Sang., 64, pp. 191-192. , BaselHoofnagle, J.H., Hepatitis C: The clinical spectrum of disease (1997) Hepatology, 26 (1 SUPPL.), pp. 15S-20SKleinman, S., Alter, H., Busch, M., Increased detection of hepatitis C virus (HCV)-infected blood donors by a multiple-antigen HCV enzyme immunoassay (1992) Transfusion, 32, pp. 805-813Kuo, G., Choo, Q.L., Alter, H.J., An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis (1989) Science, 244, pp. 362-364Lok, A.S.F., Gunaratnam, N.T., Diagnosis of hepatitis C (1997) Hepatology, 26 (1 SUPPL.), pp. 48S-56SPrati, D., Capelli, C., Zanella, A., Influence of different hepatitis C virus genotypes on the course of asymptomatic hepatitis C virus infection (1996) Gastroenterology, 100, pp. 178-183Prieto, M., Olaso, V., Verdu, C., Does the healthy hepatitis C virus carrier state really exist? An analysis using polymerase chain reaction (1995) Hepatology, 22, pp. 413-417Prince, A.M., Brotman, B., Inchauspe, G., Patterns and prevalence of hepatitis C virus infection in posttransfusion non-A, non-B hepatitis (1993) J. Infect.Dis, 167, pp. 1296-1301Rossini, A., Gazzola, G.B., Ravaggi, A., Long-term follow-up and infectivity in blood donors with hepatitis C antibodies and persistently normal alanine aminotransferase levels (1995) Transfusion, 35, pp. 108-111Salmeron, F.J., Palacios, A., Perez-Ruiz, M., Epidemiology, serological markers, and hepatic disease of anti-HCV ELISA-2 positive blood donors (1996) Dig. Dis. Sci., 41, pp. 1933-1938Schiff, E.R., Hepatitis C and alcohol (1997) Hepatology, 26 (1 SUPPL.), pp. 39S-42SSerfaty, L., Nousbaum, J.R., Elghouzzi, M.H., Prevalence, severity, and risk factors of liver disease in blood donors positive in a second-generation anti-hepatitis C virus screening test (1995) Hepatology, 21, pp. 725-729Shakil, A.O., Conry-Cantilena, C., Alter, H.J., Volunteer blood donors with antibody to hepatitis C virus: Clinical, biochemical, virologic and histologic features (1995) Ann. Intern. Med., 123, pp. 330-337Sharara, A.I., Hunt, C.M., Hamilton, J.D., Hepatitis C (1996) Ann. Intern. Med., 125, pp. 658-668Ulrich, P., Romeo, J., Lane, P., Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase (1990) J. Clin. Invest., 86, pp. 1609-161

Application of the bar score as a predictor of short- and long-term survival in liver transplantation patients

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The balance of risk (BAR) is a prediction system after liver transplantation. To assess the BAR system, a retrospective observational study was performed in 402 patients who had transplant surgery between 1997 and 2012. The BAR score was computed for each patient. Receiver operating characteristic curve analysis with the Hosmer-Lemeshow test was used to calculate sensitivity, specificity, and model calibration. The cutoff value with the best Youden index was selected. Statistical analysis employed the Kaplan-Meier method (log-rank test) for survival, the Mann-Whitney test for group comparison, and multiple logistic regression analysis. 3-month survival was 46 % for BAR a parts per thousand yen11 and 77 % for BAR 6 units (OR 2.99; 95 % CI 1.92-4.64; p = 0.001). Our study contributes to the incorporation of the BAR system into Brazilian transplantation centers.The balance of risk (BAR) is a prediction system after liver transplantation. To assess the BAR system, a retrospective observational study was performed in 402 patients who had transplant surgery between 1997 and 2012. The BAR score was computed for each91113119CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)SEM INFORMAÇÃ

Human Herpesvirus-6 And Cytomegalovirus Dna In Liver Donor Biopsies And Their Correlation With Hla Matches And Acute Cellular Rejection

Herpesvirus reactivation is common after liver transplantation. Objective: Analyze the presence of cytomegalovirus (HCMV) and human herpesvirus-6 (HHV-6) DNA in liver donor biopsies, seeking to better understand issues involving human donor leukocyte antigens (HLA)-A, B and DR, as well as correlations with acute cellular rejection. Methods: Fifty-nine liver transplantation patients were investigated for the presence of HCMV and HHV-6 DNA in liver donor biopsies, using the Nested-PCR technique. The clinical donor information and HLA matches were obtained from the São Paulo State Transplant System. The recipients' records regarding acute cellular rejection were studied. Results: Seven (11.8%) biopsies were positive for HCMV DNA and 29 (49%) were positive for HHV-6 DNA. In 14 donors with HLA-DR 15 nine had HHV-6 DNA positive liver biopsy with a tendency for significant association (p=0.09), 22 recipients developed acute cellular rejection and 9/22 were positive for HLA-DR 15 (p=0.03; χ2=4.51), which was statistically significant in univariate analysis and showed a tendency after multivariate analysis (p=0.08). Conclusion: HHV-6 DNA was prevalent in liver donors studied as well as HLA-DR 15. These findings suggest that patients with HLA-DR 15 in liver donor biopsies develop more rejection after liver transplantation. © 2013 Elsevier Editora Ltda.182220224Cope, A.V., Sabin, C., Burroughs, A., Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation (1997) J Infect Dis, 176, pp. 1484-1490Razonable, R.R., Lautenschlager, I., Impact of human herpes virus 6 in liver transplantation (2010) World J Hepatol, 2, pp. 345-353Beam, E., Razonable, R.R., Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment (2012) Curr Infect Dis Rep, 14, pp. 633-641Manez, R., White, L.T., Linden, P., The influence of HLA matching on cytomegalovirus hepatitis and chronic rejection after liver transplantation (1993) Transplantation, 55, pp. 1067-1071Seehofer, D., Rayes, N., Tullius, S.G., CMV hepatitis after liver transplantation: incidence, clinical course, and long-term follow-up (2002) Liver Transpl, 8, pp. 1138-1146Lan, X., Zhang, M.M., Pu, C.L., Impact of human leukocyte antigen mismatching on outcomes of liver transplantation: a meta-analysis (2010) World J Gastroenterol, 16, pp. 3457-3464Guardia, A.C., Stucchi, R.S., Sampaio, A.M., Human herpesvirus 6 in donor biopsies associated with the incidence of clinical cytomegalovirus disease and hepatitis C virus recurrence (2012) Int J Infect Dis, 16, pp. 124-129Banff schema for grading liver allograft rejection: an international consensus document (1997) Hepatology, 25, pp. 658-663Shibata, D., Martin, W.J., Appleman, M.D., Detection of cytomegalovirus DNA in peripheral blood of patients infected with human immunodeficiency virus (1988) J Infect Dis, 158, pp. 1185-1192Secchiero, P., Carrigan, D.R., Asano, Y., Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction (1995) J Infect Dis, 171, pp. 273-280Guardia-Silva, A.C., Stucchi, R.S., Sampaio, A.M., Detection of cytomegalovirus and human herpesvirus-6 DNA in liver biopsy specimens and their correlation with rejection after liver transplantation (2012) Transplant Proc, 44, pp. 2441-2444Sampaio, A.M., Guardia, A.C., Milan, A., Co-infection and clinical impact of human herpesvirus 5 and 6 in liver transplantation (2012) Transplant Proc, 44, pp. 2455-2458Milan, A., Sampaio, A.M., Guardia, A.C., Monitoring and detection of cytomegalovirus in liver transplant recipients (2011) Transplant Proc, 43, pp. 1360-1361Abdel Massih, R.C., Razonable, R.R., Human herpesvirus 6 infections after liver transplantation (2009) World J Gastroenterol, 15, pp. 2561-2569Humar, A., Kumar, D., Raboud, J., Interactions between cytomegalovirus, human herpesvirus-6, and the recurrence of hepatitis C after liver transplantation (2002) Am J Transplant, 2, pp. 461-466Krueger, G.R., Klueppenberg, U., Hoffman, A., Clinical correlates of infection with human herpesvirus-6 (1994) In Vivo, 8, pp. 457-516De Bolle, L., Naesens, L., De Clercq, E., Update on human herpesvirus 6 biology, clinical features, and therapy (2005) Clin Microbiol Rev, 18, pp. 217-245Pischke, S., Gösling, J., Engelmann, I., High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis (2012) J Hepatol, 56, pp. 1063-1069Hu, J., Meng, X., Zhao, H., Association of human cytomegalovirus viremia with human leukocyte antigens in liver transplantation recipients (2011) Acta Biochim Biophys Sin (Shanghai), 43, pp. 576-581Donaldson, P., Underhill, J., Doherty, D., Influence of human leucocytes antigen matching on liver allograft survival and rejection: 'the dualistic effect' (1993) Hepatology, 17, pp. 1008-101

Treatment of hepatitis C virus genotype 3 infection with direct-acting antiviral agents

Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of direct-acting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83–100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contraindications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82–96% among patients without cirrhosis and 62–92% among those with cirrhosis. Finally, SOF plus DCV provides 94–97% SVR rates in non-cirrhotic patients, but 59–69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection

Is isoniazid safe for liver transplant candidates with latent tuberculosis?

Isoniazid (INH) is recommended for tuberculosis prophylaxis in non–liver transplant recipients. However, there is a great reluctance to prescribe this agent for liver transplant candidates and recipients due to the risk of precipitating further hepatic decompensation. We analyzed the records of liver transplantation candidates undergoing a purified protein derivative (PPD) test (tuberculosis skin test) between 2008 and 2010. Patients with no respiratory symptoms, PPD test > 10 mm, and normal chest radiography were diagnosed as latent tuberculosis and prescribed INH (300 mg) per day for 6 months. The 191 patients submitted to a PPD test and those on tuberculosis prophylaxis underwent blood tests and clinical evaluations monthly to detect hepatotoxicity of patients The 33 subjects (17.2%) with a PPD test ≥ 10 mm displayed an average Model for End-stage Liver Disease score of 20 (range: 9–29) and Child-Pugh A/B score. The main causes for liver disease were chronic hepatitis C, hepatocellular carcinoma, and alcohol abuse. Among 27 patients who received INH, 18 (66.6%) completed 6 months of prophylaxis. Eight who had shorter treatment courses of 2 to 4 months had undergone transplantation. One patient had to stop treatment because of clinical decompensation due to spontaneous bacterial peritonitis without a transaminases elevation. Six patients did not receive INH: previous tuberculosis treatment, transplantation before initiating prophylaxis, or removal from the liver candidacy list. No patient showed clinical decompensation or laboratory abnormalities associated with use of INH. The average values of alanine aminotransferase pre- and posttreatment were similar (69 and 72 U/l respectively), demonstrating that tuberculosis prophylaxis with INH was safe for liver transplant candidates4482406241

Elevated Alanine Aminotransferase (alt) In Blood Donors : An Assessment Of The Main Associated Conditions And Its Relationship To The Development Of Hepatitis C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/ 101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.404219224Aach, R.D., Szmuness, W., Mosley, J.W., Serum alanine aminotransferase of donors in relation to the risk of non-A, non-B hepatitis in recipients (1981) New Engl. J. Med., 304, pp. 989-994Alter, H.J., Purcell, R.H., Holland, P.V., Alling, D.W., Koziol, D.E., Donors transaminase and recipient hepatitis. Impact on blood transfusion services (1981) J. Amer. Med. Ass., 246, pp. 630-634Alter, H.J., The cloning and clinical implications of HGV and HGBV-C (1996) New Engl. J. Med., 334, pp. 1536-1537Alter, H.J., Transfusion transmitted hepatitis C and non-A, non-B, non-C (1994) Vox Sang. (Basel), 67, pp. 19-24Alter, M.J., Hadler, S.C., Judson, F.N., Risk factors for acute non-A,non-B hepatitis in the United States and association with hepatitis C virus infection (1990) J. Amer. Med. Ass., 264, pp. 2231-2235Alter, M.J., Margolis, H.S., Krawczynski, K., The natural history of community-acquired hepatitis C in the United States (1992) New Engl. J. Med., 327, pp. 1899-1905Busch, M.P., Korelitz, J.J., Kleinman, S.H., Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. The Retrovirus epidemiology donor study (1995) Transfusion, 35, pp. 903-910Chomczynski, P., Sacchi, N., Single step method of RNA isolation by acid guanidium thyocyanate-phenol-chloroform extraction (1987) Analyt. Biochem., 162, pp. 156-159Choo, Q.L., Kuo, G., Weiner, A.J., Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome (1989) Science, 244, pp. 359-362Choudhury, N., Ramesh, V., Saraswat, S., Naik, S., Effectiveness of mandatory transmissible diseases screening in Indian blood donors (1995) Indian J. Med. Res., 101, pp. 229-232De Lamballerie, X., Charrel, R.N., Bussol, B., Hepatitis GB virus C in patients on hemodialysis (1996) New Engl. J. Med., 335, p. 1549Friedman, L.S., Dienstag, J.L., Walkins, E., Evaluation of blood donors with elevated serum alanine aminotransferase levels (1987) Ann. Intern. Med., 107, pp. 137-144Garrow, J.S., (1988) Obesity and Related Diseases, , New York, Churchill LivingstoneGarson, J.A., Tedder, R.S., Briggs, M., Detection of hepatitis C viral sequences in blood donations by "nested" polymerase chain reaction and prediction of infectivity (1990) Lancet, 335, pp. 1419-1422Gonçales Jr., F.L., Boccato, R.S.B.S., Pedro, R.J., Prevalências do HBsAg, do anti-HBc e do anti-HCV na população de candidatos a doadores de sangue do Hemocentro-Campinas (1993) Rev. Inst. Med. Trop. S. Paulo, 35, pp. 45-51Gonçales Jr., F.L., Pedro, R.J., Silva, L.J., Hepatites póstransfusionais na cidade de Campinas, SP, Brasil. II. Presença dos anticorpos anti-HBc e anti-HCV em candidatos a doadores de sangue e ocorrência de hepatites pós-transfusionais pelo virus C nos receptores de sangue ou derivados (1993) Rev. Inst. Med. Trop. S. Paulo, 35, pp. 63-71Gonçales Jr., F.L., Pedro, R.J., Silva, L.J., Hepatites póstransfusionais na cidade de Campinas, SP, Brasil. I. Incidência, agentes etiológicos e aspectos clínico-epidemiológicos da hepatite por virus C (1993) Rev. Inst. Med. Trop. S. Paulo, 35, pp. 53-62Hultcrantz, R., Glaumann, H., Lindberg, G., Nilsson, L.H., Liver investigation in 149 asymptomatic patients with moderately elevated activities of serum aminotransferases (1986) Scand. J. Gastroent., 21, p. 109Ismay, S.L., Thomas, S., Fellows, A., Post-transfusion hepatitis revisited (1995) Med. J. Aust., 163, pp. 74-77Jullien, A.M., Courouce, A.M., Massari, V., Impact of screening donor blood for alanine aminotransferase and antibody to hepatitis B core antigen on the risk of hepatitis C virus transmission (1993) Europ. J. Clin. Microbiol. Infect. Dis., 12, pp. 668-672Kahn, R.A., Johnson, G., Aach, R.D., The distribution of serum alanine aminotransferase levels in a blood donor population (1982) Amer. J. Epidem., 115, pp. 929-940Katkov, W.N., Friedman, L.S., Cody, H., Elevated serum alanine aminotransferase levels in blood donors:the contribution of hepatitis C virus (1991) Ann. Intern. Med., 115, pp. 882-884Krawczynski, K., Hepatitis E: Clinical course and prevention (1994) Postgraduate Course - Viral Hepatitis A to F: An Update, pp. 83-91. , AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES. Chicago, AASLDKuo, G., Choo, Q.-L., Alter, H.J., An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis (1989) Science, 244, pp. 362-364Larrey, D., Rueff, B., Pessayre, D., Cross hepatotoxicity between tricyclic antidepressants (1986) Gut, 27, pp. 726-727Leary, T.P., Muerhoff, A.S., Simons, J.N., Consensus oligonucleotides primers for the detection of GB virus C in human cryptogenic hepatitis (1996) J. Virol. Meth., 59, pp. 119-121Linnen, J., Wages Jr., J., Zhang-Keck, Z.-Y., Molecular cloning and disease association of hepatitis G virus: A transfusion-transmissible agent (1996) Science, 271, pp. 505-508Love, E., Pendry, K., Hunt, L., Analysis of pre- and post-donation haematological values in plateletpheresis donors (1993) Vox Sang. (Basel), 65, pp. 209-211Masuko, K., Mitsui, T., Iwano, K., Infection with hepatitis GB virus C in patients on maintenance hemodialysis (1996) New Engl. J. Med., 334, pp. 1485-1490Menghini, G., One-second needle biopsy of the liver (1958) Gastroenterology, 35, p. 190Moatter, T., Tariq, S.A., Fisher-Hoch, S., Hepatitis G virus in Karachi,Pakistan (1996) Lancet, 348, pp. 1318-1319Moaven, L.D., Hyland, C.A., Young, I.F., Prevalence of hepatitis G virus in Queensland blood donors (1996) Med. J. Aust., 165, pp. 369-371Consensus development panel on infectious disease testing for blood transfusions: Infectious disease testing for blood transfusions (1995) J. Amer. Med. Ass., 274, pp. 1374-1379Palmer, M., Schaffner, F., Effect of weight reduction on hepatic abnormalities in overweight patients (1990) Gastroenterology, 99, pp. 1408-1413Popper, H., Schaffner, F., The vocabulary of chronic hepatitis (1971) New Engl. J. Med., 284, pp. 1154-1156Ravaggi, A., Primi, D., Cariani, E., Direct PCR amplification of HCV RNA from humam serum (1992) PCR Meth. Applic., 1, pp. 291-292Sherman, K.E., Dodd, R.Y., Alanine aminotransferase levels among volunteer blood donors: Geographic variation and risk factors (1982) J. Infect. Dis., 145, pp. 383-386Simons, J.N., Leary, T.P., Dawson, G.J., Isolation of novel virus -like sequences associated with human hepatitis (1995) Nature Med., 1, pp. 564-569Simons, J.N., Pilot-Matias, T.N., Leary, T.P., Identification of two flavivirus-like genomes in the G B hepatitis agent (1995) Proc. Nat. Acad. Sci. (Wash.), 92, pp. 3401-3405Vanderborght, B.O., Reis, A.M., Rouzere, C.D., Prevalence of anti-hepatitis C virus in the blood donor population of Rio de Janeiro (1993) Vox Sang. (Basel), 65, pp. 122-12

Brazilian Spotted Fever: A Case Series From An Endemic Area In Southeastern Brazil. Epidemiological Aspects

Brazilian spotted fever (BSF) is the most important tick-borne disease in Brazil and is caused by Rickettsia rickettsii and transmitted by the Ixodid tick Amblyomma cajennense, its main vector. We present epidemiologic aspects of a case series of patients admitted to the Hospital das Clinicas da UNICAMP from 1985 to 2003 with a confirmed diagnosis of BSF either by a fourfold rise in indirect immunofluorescence (IFA) titers of IgG antibodies reactive with R. rickettsii or isolation of R. rickettsii from blood or skin specimens. Seasonal variation of case occurrence seems to be associated with the life cycle of the tick. The recent reemergence of cases seems to be associated with the growing numbers of the capybara (Hydrochaeris hydrochaeris) and their expansion into urban areas. © 2006 New York Academy of Sciences.1078170172Sangioni, L.A., Horta, M.C., Vianna, M.C., Rickettsial infection in animals and Brazilian Spotted Fever endemicity (2005) Emerg. Inf. Dis., 11, pp. 265-270Lemos, E.R.S., Alvarenga, F.B.F., Cintra, M., Spotted fever in Brazil: An epidemiological study and description of clinical cases in an endemic area in the state of São Paulo (2001) Am. J. Trop. Med. Hyg., 65, pp. 329-334Horta, M.C., Labruna, M.B., Sangioni, L.A., Prevalence of antibodies to spotted fever group rickettsiae in humans and domestic animals in a Brazilian Spotted Fever endemic area in the state of São Paulo, Brazil: Serologic evidence for infection by Rickettsia rickettsii and other Spotted Fever Group rickettsia (2004) Am. J. Trop. Med. Hyg., 71, pp. 93-97Dias, E., Martins, A.V., Spotted fever in Brazil: A summary (1939) Am. J. Trop. Med., 19, pp. 103-108Gaevão, M.A.M., Dumler, J.S., Mafra, C.L., Fatal spotted fever rickettsiosis, Minas Gerais, Brazil (2003) Emerg. Inf. Dis., 9, pp. 1402-1405Lima, V.L.C., Souza, S.S.L., Souza, C.E., Spotted fever in Campinas region, State of São Paulo, Brazil (2003) Cad. Saúde Públ., 19, pp. 331-334Thorner, A.R., Walker, D.H., Petri, W.A., Rocky Mountain spotted fever (1998) Clin. Inf. Dis., 27, pp. 1353-1360Febre Maculosa, , http://www.cve.saude.sp.gov.br/htm/Cve_fmaculosa.htm, Available at [accessed in July 30, 2005