Clara Fumiko Tachibana Yoshida

Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

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Publications (113)228.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-human primates have been playing an essential role in the study of hepatitis A virus (HAV) biology, pathogenesis and for testing candidate HAV vaccines. This study was to determine the suitability of squirrel monkeys (Saimiri sciureus) as animal model for HAV infection. Animals were inoculated, either intragastrically or intravenously, with a Brazilian HAV isolate (HAF-203). Alanine aminotransferase (ALT) and anti-HAV antibodies (IgM and total) were monitored. Feces were daily collected for HAV antigen and HAV RNA detection. Samples of liver tissue were obtained by biopsy before inoculation at peak ALT levels and/or when anti-HAV antibodies developed, and at necropsy for morphological examination. Monkeys inoculated by the intravenous route rapidly developed significant elevations of serum ALT, anti-HAV antibodies, and liver histologic changes, while the only evidence of HAV infection in intragastrically inoculated animals was the seroconversion. Moreover, squirrel monkeys excreted very low levels of HAV detectable in only few fecal samples after amplification by RT-PCR, different from humans and other non-human primate species that eliminate large quantities of virus during the late incubation period. The unusual onset of hepatitis A in experimentally infected squirrel monkeys represent an important obstacle for its use as animal model for the study of this viral infection. However, they can represent a valuable tool for the obtention of hyperimmune sera for HAV, in the view of the very high titer of anti-HAV developed (105) 24 days after a single intravenous inoculation.
    Primates 04/2012; 41(2):127-135. DOI:10.1007/BF02557794 · 1.40 Impact Factor
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    ABSTRACT: Detection of hepatitis B virus (HBV) serological markers in dried blood spot (DBS) samples by enzyme immunoassay (ELISA) has not yet been fully optimized. In this study, the ability to detect three HBV markers (HBsAg, anti-HBc, and anti-HBs) was evaluated in DBS samples using a modified commercial ELISA. Matched serum and DBS samples were obtained from individuals with or without a past history of HBV infection. Sera samples were tested according to the manufacturer's instructions, but for DBS testing, paper diameters, elution buffer, volume of input sample, and cut-off values were evaluated to optimize the assay. Stability studies were done on DBS stored at for up to 180 days at different temperatures. The absorbance values that yielded the maximum sensitivity and specificity were determined based on the area under the ROC curve (AUROC) and chosen as the cut-off value. Using this parameter, sensitivity was 90.5%, 97.6%, and 78% for anti-HBc, HBsAg, anti-HBs assays, respectively. Specificity was 92.6%, 96.7%, and 97.3% for anti-HBc, HBsAg, and anti-HBs assays, respectively. HBV markers could be detected in DBS samples until 63 days after sample collection at most temperatures, but storage at -20°C yielded more consistent results. These results indicate that modified ELISA can be used to detect HBV markers in DBS samples, particularly if the samples are stored appropriately.
    Journal of Medical Virology 09/2011; 83(9):1522-9. DOI:10.1002/jmv.22138 · 2.22 Impact Factor
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    ABSTRACT: The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period. We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up. Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001]. Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection.
    BMC Infectious Diseases 01/2011; 11:15. DOI:10.1186/1471-2334-11-15 · 2.61 Impact Factor
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    ABSTRACT: In this study, a modified enzyme immunoassay (EIA) was evaluated for the Hepatitis B surface antigen (HBsAg) among whole saliva and oral fluid samples. Specimens were collected from 115 individuals who gave serum and oral fluid using Salivette (Sarstedt, Nümbrecht, Germany) and whole saliva. Saliva specimens were tested following a modified ELISA, and the results were compared with paired serum specimens that were tested according to the supplier's instructions. Transport buffer for the oral fluids, sample volume for assay, incubation period of sample with conjugate as well as cut-off values were evaluated to optimize the assay. The highest sensitivity and specificity were obtained by increasing the incubation of sample and conjugate to 16  hr and using the area under the receiver operating characteristic curve to calculate cut-off values. HBsAg was detected in 40 oral fluids and 44 whole saliva samples out of 47 paired positive serum specimens and not detected in 64 oral fluids and 63 whole saliva samples out of 68 matched negative sera samples by the ELISA assay. There was excellent agreement between the results for the serum and saliva specimens kappa value (κ): 0.80 for oral fluid and κ: 0.87 for whole saliva and there was excellent reproducibility. Using an optimized protocol, the sensitivities of whole saliva and oral fluid were 93.6 and 85.1%, respectively, whereas specificities of whole saliva and oral fluid were 92.6 and 94.1%, respectively. Our data showed a significant promise for the use of whole saliva and oral fluid together with the modified commercial EIA for Hepatitis B virus infection surveillance.
    Journal of Clinical Laboratory Analysis 01/2011; 25(2):134-41. DOI:10.1002/jcla.20447 · 1.14 Impact Factor
  • Journal of Hepatology 04/2010; 52. DOI:10.1016/S0168-8278(10)60636-8 · 10.40 Impact Factor
  • Journal of Hepatology 04/2010; 52. DOI:10.1016/S0168-8278(10)60637-X · 10.40 Impact Factor
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    ABSTRACT: The natural outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. However, little is known about host and viral factors associated with a self-limiting or chronic evolution of HCV infection. From 1 January 2001 through 31 December 2008, a consecutive series of 65 patients from Rio de Janeiro, Brazil, with a well-documented diagnosis of acute HCV infection, acquired via various routes, were enrolled in this study. Patients were prospectively followed up for a median of 40 months after the estimated date of HCV infection with serial measurements of serum alanine aminotransferase, HCV RNA, and anti-HCV antibodies. Spontaneous viral clearance (SVC) was defined as undetectable levels of HCV RNA in serum, in the absence of treatment, for 3 consecutive HCV polymerase chain reaction tests within the first 6 months of follow-up. Cox proportional hazards regression was used to identify host and viral predictors of SVC. The cumulative rate of SVC was 44.6% (95% confidence interval, 32.3%-57.5%). Compared with chronic HCV evolution, patients with self-limiting disease had significantly lower peak levels of anti-HCV antibodies (median, 109.0 vs 86.7 optical density-to-cutoff ratio [od/co]; P<.02), experienced disease symptoms more frequently (69.4% vs 100%; P<.001), and had lower viral load at first clinical presentation (median, 4.3 vs 0.0 log copies; P=.01). In multivariate analyses, low peak anti-HCV level (<93.5 od/co) was the only independent predictor for SVC; the hazard ratio compared with high anti-HCV levels (> or =93.5 od/co) was 2.62 (95% confidence interval, 1.11-6.19; P=.03). Our data suggest that low levels of anti-HCV antibodies during the acute phase of HCV infection are independently related to spontaneous viral clearance.
    Clinical Infectious Diseases 03/2010; 50(9):1222-30. DOI:10.1086/651599 · 9.42 Impact Factor
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    Viviana Ré · Marta Contigiani · Clara Fumiko Tachibana Yoshida · Elisabeth Lampe
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    ABSTRACT: In Argentina, most information on hepatitis C virus (HCV) genotype distribution comes from studies carried out in Buenos Aires (east province). In order to identify HCV subtypes in central Argentina, nucleotide sequencing of core region was performed in samples from 36 patients living in Córdoba, the second most populated province of Argentina. The sequence analysis identified subtype 2c as the most prevalent (50%), followed by subtype 1b (33%) and to a lesser extent by subtypes 1a (11%), 3a (3%) and 4a (3%). This is the first report of circulation of HCV subtype 2c in this region of Argentina and also such high prevalence has never been found before in the genotype distribution of South America.
  • 07/2009; 38(2). DOI:10.5216/rpt.v38i2.6627
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    ABSTRACT: In the last decade, a declining prevalence of HCV infection has been described in injecting drug users (IDUs) in different countries. This study is the first to assess temporal trends in drug-injecting patterns, HCV infection rates and viral genotype distribution in 770 Brazilian IDUs, recruited by two cross-sectional studies (1994-1997 and 1999-2001). A substantial decline in the prevalence of HCV infection was found over the years (75% in 1994 vs. 20.6% in 2001, P<0.001) that may be a consequence of the significant reduction in the overall frequencies of drug injection and needle-sharing, as well as the participation of IDUs in initiatives aimed at reducing drug-related harm. No trend was found in terms of viral genotype distribution. Despite the favourable scenario, preventive measures must be maintained, especially in vulnerable subgroups such as young or new injectors, where risky behaviours through direct and indirect sharing practices remain common.
    Epidemiology and Infection 07/2009; 137(7):970-9. DOI:10.1017/S0950268808001970 · 2.49 Impact Factor
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    ABSTRACT: Compliance with and responses to the hepatitis B vaccine were evaluated in remaining quilombo communities in Central Brazil. A total of 708 individuals who were susceptible to hepatitis B virus infection were invited to participate in the hepatitis B vaccination program in eight communities. Although 567 (80%) individuals received the first dose, only 198 (28%) complied with the full vaccination scheme. Of 148 subjects who agreed to be tested for anti-HBs, 123 (83.1%; 95%CI: 75.9-88.6) responded to the vaccine. A geometric mean titer of 512mIU/mL (95%CI: 342.5-765.3) was found. Male sex and older age were independently associated with non-response. Additional health education programs and alternative hepatitis B vaccine schedules are needed to improve the vaccination coverage in these communities in Central Brazil.
    Cadernos de saúde pública / Ministério da Saúde, Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública 05/2009; 25(4):738-42. DOI:10.1590/S0102-311X2009000400004 · 0.89 Impact Factor
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    ABSTRACT: Since the identification of hepatitis C virus (HCV) in 1989 as a causative agent for a number of the extrahepatic alterations related to HCV infection an underlying immune mediated pathogenetic mechanism has been postulated. HCV-associated thrombocytopenia may be considered complex and multifactorial in origin, since different mechanisms have been implicated in its pathophysiology. With respect to autoimmune thrombocytopenia in chronic HCV infection, the detection of specific antibodies against platelet glycoproteins have been reported only in a few studies, but no systematic study has been carried out. We examined the clinical, laboratory, and virological characteristics of a case series of 10 patients with autoimmune thrombocytopenia (platelet count <150.0 x 10(9)/L) related to chronic HCV infection. Cases, six males and four females, aged 57.1 +/- 12.6 years, presented high titers of antibodies against platelet glycoprotein (GP) IIb/IIIa, GP Ia/IIa, and/or GP Ib/IX, and no other mechanism involved in the pathogenesis of HCV-associated thrombocytopenia was identified. Furthermore, cases were not associated with particular HCV genotype. Complete platelet response was observed in two patients treated with pegylated interferon plus ribavirin, and partial platelet response was seen in two patients treated with anti-D Ig and one patient treated with corticosteroids. These findings indicate that an autoimmune mechanism may play a role in the pathogenesis of HCV-associated thrombocytopenia in a proportion of these patients.
    Hematology (Amsterdam, Netherlands) 03/2009; 14(1):49-58. DOI:10.1179/102453309X385106 · 1.19 Impact Factor
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    ABSTRACT: Injecting drug users (IDU) have a key role in Hepatitis C Virus (HCV) epidemiology. Young/short-term IDUs constitute a target group for preventive/harm reduction interventions. To investigate HCV transmission among young/short-term (ST) and long-term (LT) IDUs, from the perspective of epidemiology and molecular biology. Cross-sectional study assessing the prevalence of HCV infection/genotypes, as well as risk behaviours/practices among IDUs from Rio de Janeiro. Phylogenetic analyses were performed and the extent of segregation between sequences was quantified by the Association Index. ST were more likely to engage into needle-sharing (p=.021) and LT to attend Needle Exchange Programs (p=.006). HCV prevalence was 10.1% vs. 23.4% among initiates and LT, respectively (p<.001). Older age vs. imprisonment and longer duration of IDU career were independent predictors for HCV infection among ST and LT, respectively. Among the latter, NEP attendance was inversely associated with viral infection. HCV3a infections were the most prevalent. A moderate extent of phylogenetic segregation between sequences was found, suggestive of transmission between IDU subgroups. The lower HCV prevalence among young/short-term IDUs cannot be viewed with complacency, due to their frequent engagement into direct/indirect sharing practices and the ongoing transmission between IDU subsets. To avert new infections, preventive/harm reduction policies must be tailored to empirical findings.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 02/2009; 44(3):200-6. DOI:10.1016/j.jcv.2008.12.008 · 3.47 Impact Factor
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    ABSTRACT: This article aimed to estimate the prevalence of hepatitis C in Botafogo, a district of Bebedouro, São Paulo State, Brazil, and investigate possible risk factors. One individual over 18 years of age was selected from each household to answer a questionnaire on socio-demographic variables and factors associated with hepatitis C. Blood samples were also drawn for immunoenzymatic tests. Positive HCV-antibody samples were submitted to viral RNA detection. HCV prevalence was 8.8% (95%CI: 5.8-11.7), and independent variables associated with risk of infection were: male gender, time of local residence > 30 years, and history of injected medication using non-disposable material, sterilized by boiling. The high prevalence of hepatitis C infection in this relatively isolated rural population appears to result from previous exposure to injections with inadequately sterilized material, with some evidence suggesting a specific elderly pharmacy employee who customarily applied such injections and may have been a chronic HCV carrier.
    Cadernos de saúde pública / Ministério da Saúde, Fundação Oswaldo Cruz, Escola Nacional de Saúde Pública 02/2009; 25(2):460-4. · 0.89 Impact Factor
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    ABSTRACT: Detection of HCV has been documented in extrahepatic sites such as platelets. However, its influence on antiviral therapy outcome is unknown. In this study, we investigated the relationship between the detection of HCV in platelets from a cohort of 48 chronically HCV-infected patients and response to antiviral therapy. This study comprised of 19 males and 29 females, mean age 54.9 +/- 8.72 years, followed-up in Rio de Janeiro, Brazil, between August 2004 and October 2006. HCV-RNA was detected in serum and platelets (pre-treatment, end-of-treatment and 24 weeks after completion of therapy) by reverse transcription-nested polymerase chain reaction. Patients with genotype 1 or 4 were treated with peginterferon-alfa/ribavirin for 48 weeks, and patients with genotype 3 received interferon-alfa/ribavirin for 24 weeks. Baseline detection of HCV in platelets was found not to be related to therapy outcome. However, significant associations between detection rates of HCV in platelets and serum at the end-of-treatment (p = 0.0203), and 24 weeks after completion of therapy (p = 0.0016) were observed. Interestingly, HCV was detected in platelets from two patients with normal ALT who lost detectable serum HCV at the end-of-treatment and, after 24 weeks of followup, relapsed virologically in serum. Our data suggest that patients with HCV persistence in platelets by the end-of-treatment appear to be at an increased risk of recurrent HCV infection.
    Hepato-gastroenterology 01/2009; 56(90):429-36. · 0.91 Impact Factor
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    ABSTRACT: In order to determine the prevalence of hepatitis C virus (HCV) infection in quilombo remnant communities in Central Brazil, 1,007 subjects were interviewed in all 12 communities existing in Mato Grosso do Sul State, Central Brazil. Blood samples were collected and sera were tested for anti-HCV by enzyme-linked immunosorbent assay. Positive samples were retested for confirmation using a line immunoassay and were also subjected to HCV RNA detection. The prevalence of HCV infection was 0.2%. This finding shows a low prevalence of HCV infection in quilombo remnant communities in Central Brazil.
    Revista do Instituto de Medicina Tropical de São Paulo 11/2008; 50(6):359-60. DOI:10.1590/S0036-46652008000600010 · 0.91 Impact Factor
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    ABSTRACT: An investigation was conducted involving 255 renal transplant recipients in the state of Goiás, Central Brazil, to determine the prevalence of hepatitis C virus (HCV), its risk factors, the genotypes involved, and the level of alanine aminotransferase (ALT) present in the patients. All serum samples were tested for anti-HCV antibodies and HCV RNA. Forty-one patients were anti-HCV and/or HCV RNA positive, resulting in an overall HCV infection prevalence of 16.1% (95% CI: 11.9-21.3). A multivariate analysis of risk factors showed that a history of blood transfusions without anti-HCV screening, the length of time spent on hemodialysis, and renal transplantation before 1994 are all associated with HCV positivity. In HCV-positive patients, only 12.2% had ALT levels above normal. Twenty-eight samples were genotyped as genotype 1, subtypes 1a (62.5%) and 1b (31.3%), and two samples (6.2%) were genotype 3, subtype 3a. These data show a high prevalence of HCV infection and low ALT levels in the studied population. The risk factor analysis findings emphasize the importance of public health strategies such as anti-HCV screening of candidate blood and organ donors, in addition to the stricter adoption of hemodialysis-specific infection control measures. The present study also demonstrates that HCV genotype 1 (subtype 1a) is predominant in this population.
    Memórias do Instituto Oswaldo Cruz 09/2008; 103(5):472-6. DOI:10.1590/S0074-02762008000500011 · 1.57 Impact Factor
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    ABSTRACT: Haemodialysis (HD) continues to carry the risk of hepatitis C virus (HCV) transmission, with delayed seroconversion and often normal alanine aminotransferase (ALT) values increasing the likelihood of undetected infection and thus uninterrupted spread of HCV. The aim of this study was to identify the characteristic patterns of ALT changes and seroconversion during an outbreak of HCV in a HD unit. We also wanted to establish the relationship between infecting viruses using molecular analysis. All patients (n = 72) and staff (n = 23) of the HD unit were prospectively followed for 14 months. Serial measurements for ALT, HCV antibody and HCV-RNA were performed besides HCV sequence analysis. The initial screening for anti-HCV and HCV-RNA confirmed chronic infection in 16/72 (22%) subjects and identified three subjects with recent seroconversion. In addition, five cases were reverse transcription-polymerase chain reaction positive alone for a total of eight recent cases. The interval between the initial observation of ALT changes and seroconversion varied from 1 to 8 months, and in several individuals ALT fluctuations only below the upper limit of normal were detected. However, relating each subject's ALT values to ALT at baseline, ALT levels increased between 1.6- and 4.7-fold. Molecular analysis provided evidence for transmission from two chronically infected source patients, probably because of inappropriate infection control measures. Our data highlight the importance of well-implemented safety precautions and regular HCV-RNA testing to prevent the further spread of HCV in this population, and suggest the use of ALT baseline values to identify infections that may remain unnoticed otherwise.
    Nephrology 07/2008; 13(3):186-92. DOI:10.1111/j.1440-1797.2008.00931.x · 1.86 Impact Factor
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    Viviana Ré · Marta Contigiani · Clara Fumiko Tachibana Yoshida · Elisabeth Lampe
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    ABSTRACT: In Argentina, most information on hepatitis C virus (HCV) genotype distribution comes from studies carried out in Buenos Aires (east province). In order to identify HCV subtypes in central Argentina, nucleotide sequencing of core region was performed in samples from 36 patients living in Córdoba, the second most populated province of Argentina. The sequence analysis identified subtype 2c as the most prevalent (50%), followed by subtype 1b (33%) and to a lesser extent by subtypes 1a (11%), 3a (3%) and 4a (3%). This is the first report of circulation of HCV subtype 2c in this region of Argentina and also such high prevalence has never been found before in the genotype distribution of South America.
    Memórias do Instituto Oswaldo Cruz 01/2008; 102(8):995-8. DOI:10.1590/S0074-02762007000800016 · 1.57 Impact Factor

Publication Stats

1k Citations
228.45 Total Impact Points

Institutions

  • 1984–2012
    • Fundação Oswaldo Cruz
      • • Departamento de Virologia (CPqAM)
      • • Department of Virology (IOC)
      • • Instituto Oswaldo Cruz (IOC)
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2006
    • Rio de Janeiro State University
      Rio de Janeiro, Rio de Janeiro, Brazil
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
    • National University of Cordoba, Argentina
      Córdoba, Cordoba, Argentina
  • 2002
    • Universidade Federal de Mato Grosso do Sul
      Campo Grande, Estado de Mato Grosso do Sul, Brazil
  • 1998–2002
    • Universidade Federal de Goiás
      • Instituto de Patologia Tropical e Saúde Pública (IPTSP)
      Goiânia, Estado de Goias, Brazil
  • 2001
    • Harvard University
      Cambridge, Massachusetts, United States
    • Federal University of Pará
      • Department of Pathology
      Pará, Pará, Brazil
  • 2000
    • University of São Paulo
      San Paulo, São Paulo, Brazil
  • 1996
    • Beijing Medical University
      • Institute of Hepatology
      Peping, Beijing, China