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1.
Epidemiol Infect ; 148: e53, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32070438

RESUMO

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the 'Fiebig staging system' has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying 'sensitivity'. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define 'stages' of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.


Assuntos
Infecções por HIV/diagnóstico , Diagnóstico Tardio , Diagnóstico Precoce , Anticorpos Anti-HIV/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Modelos Biológicos , Prognóstico , Índice de Gravidade de Doença , Carga Viral/estatística & dados numéricos
2.
Clin Microbiol Infect ; 23(12): 1001.e1-1001.e3, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28711704

RESUMO

OBJECTIVES: Zika virus (ZIKV) transmission through semen donation has never been reported but the risk is supported by the detection of ZIKV in semen and the demonstration of ZIKV sexual transmission. The potential impact of ZIKV on assisted reproductive procedures should be evaluated. METHODS: We tested longitudinally collected semen samples provided by asymptomatic blood donors who tested positive for ZIKV RNA in plasma during ZIKV outbreaks in Puerto Rico and Florida in 2016. RESULTS: Five of the 14 (35.7%) asymptomatic blood donors provided semen samples that tested positive for ZIKV RNA, with ZIKV RNA loads ranging from 8.03 × 103 to 2.55 × 106 copies/mL. Plasma collected at the same time as the semen tested negative for ZIKV RNA for most ZIKV RNA-positive semen collections; all corresponding plasma samples tested positive or equivocal for anti-ZIKV IgG antibodies and all except one tested positive for ZIKV IgM antibodies. The rate of detection of ZIKV RNA in semen in asymptomatic donors is not significantly different from the rate previously reported for symptomatic patients. CONCLUSIONS: Our results that show a high percentage of detection of ZIKV RNA in the semen of asymptomatic men confirm that ZIKV is a new threat for reproductive medicine and should have important implications for assisted reproductive technology. We recommend that semen donations from men at risk for ZIKV infection should be tested for ZIKV RNA, regardless of symptoms of ZIKV infection.


Assuntos
Doadores de Sangue , RNA Viral/genética , Sêmen/microbiologia , Infecção por Zika virus/diagnóstico , Zika virus/genética , Infecções Assintomáticas , Doadores de Sangue/estatística & dados numéricos , Florida/epidemiologia , Humanos , Masculino , Porto Rico/epidemiologia , Sêmen/química , Infecção por Zika virus/epidemiologia
3.
Epidemiol Infect ; 145(5): 925-941, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28004622

RESUMO

In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.


Assuntos
Métodos Epidemiológicos , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Recursos em Saúde , Humanos , Incidência
4.
Epidemiol Infect ; 145(12): 2536-2544, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-26829991

RESUMO

The 2012 West Nile virus (WNV) epidemic was the largest since 2003 and the North Texas region was the most heavily impacted. We conducted a serosurvey of blood donors from four counties in the Dallas-Fort Worth area to characterize the epidemic. Blood donor specimens collected in November 2012 were tested for WNV-specific antibodies. Donors positive for WNV-specific IgG, IgM, and neutralizing antibodies were considered to have been infected in 2012. This number was adjusted using a multi-step process that accounted for timing of IgM seroreversion determined from previous longitudinal studies of WNV-infected donors. Of 4971 donations screened, 139 (2·8%) were confirmed WNV IgG positive, and 69 (1·4%) had IgM indicating infection in 2012. After adjusting for timing of sampling and potential seroreversion, we estimated that 1·8% [95% confidence interval (CI) 1·5-2·2] of the adult population in the Dallas-Fort Worth area were infected during 2012. The resulting overall estimate for the ratio of infections to reported WNV neuroinvasive disease (WNND) cases was 238:1 (95% CI 192-290), with significantly increased risk of WNND in older age groups. These findings were very similar to previous estimates of infections per WNND case, indicating no change in virulence as WNV evolved into an endemic infection in the United States.


Assuntos
Epidemias , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/metabolismo , Doadores de Sangue/estatística & dados numéricos , Feminino , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Texas/epidemiologia , Febre do Nilo Ocidental/sangue , Febre do Nilo Ocidental/virologia , Adulto Jovem
5.
Vox Sang ; 111(1): 22-32, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26918437

RESUMO

BACKGROUND AND OBJECTIVES: Damage-associated molecular patterns (DAMPs) are found in transfusion products, but their potential impacts are not fully understood. We examined the influence of manufacturing method on levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in red cell concentrates (RCCs). MATERIALS AND METHODS: Eighty-seven RCCs were prepared using nine different methods (6-15 units/method), including three apheresis, five whole blood (WB)-derived leucoreduced (LR) and one WB-derived non-LR method. On storage days 5 and 42, levels of mtDNA (by PCR) and number and cell of origin of EVs (by flow cytometry) were assessed in RCC supernatants. RESULTS: There was a 100-fold difference in mtDNA levels among methods, with highest levels in non-LR, followed by MCS+ and Trima apheresis RCCs. There was a 10-fold difference in EV levels among methods. RBC-derived CD235a+ EVs were found in fresh RCCs and increased in most during storage. Platelet-derived CD41a+ EVs were highest in non-LR and Trima RCCs and did not change during storage. WBC-derived EVs were low in most RCCs; CD14+ EVs increased in several RCCs during storage. CONCLUSION: DAMPs in RCCs vary by manufacturing method. MtDNA and EV could be informative quality markers that may be relevant to RCC immunomodulatory potential.


Assuntos
Preservação de Sangue/métodos , DNA Mitocondrial/metabolismo , Eritrócitos/citologia , Mitocôndrias/genética , Remoção de Componentes Sanguíneos , DNA Mitocondrial/genética , Contagem de Eritrócitos , Eritrócitos/metabolismo , Vesículas Extracelulares/metabolismo , Citometria de Fluxo , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Selectina-P/metabolismo , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Reação em Cadeia da Polimerase , Fatores de Tempo
6.
Int J Cardiol ; 199: 451-9, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26277551

RESUMO

BACKGROUND: Chagas disease has a long clinically silent period following Trypanosoma cruzi infection and before development of overt clinical pathology; detectable biomarkers of infection and pathogenesis are urgently needed. We tested 22 biomarkers known to be associated with cardiomyopathy to evaluate if a biomarker signature could successfully classify T. cruzi seropositive subjects into clinical Chagas disease stage groups. METHODS: This cross-sectional retrospective case-control study enrolled T. cruzi seropositive blood donors (BD) who were further characterized as having chronic Chagas cardiomyopathy (CC-BD) or not (nonCC-BD) and seronegative (SN) control donors; we also included clinically diagnosed Chagas cardiomyopathy patients (CC-P). All subjects underwent a health history questionnaire, medical examination, electro- and echocardiograms (ECG and Echo) and phlebotomy. Biomarkers were measured on blinded samples by luminex bead array and Ortho VITROS. RESULTS: A clear biomarker pattern was observed only in more severe cardiac disease; this pattern included significantly elevated levels of inflammatory cytokines IFN-γ, IL-6, IL-10 and TNF-α and soluble cardiovascular disease biomarkers CK-MB, troponin, myoglobin, VCAM and NTproBNP while there were lower levels of MPO, PAI-1, and MCP-1. The markers determined to be the most predictive of disease by ROC curve analysis were NTproBNP and T. cruzi PCR status. CONCLUSIONS: Although many biomarkers demonstrated increased or decreased concentrations among the clinical forms of Chagas disease, NTproBNP and T. cruzi PCR were the only tests that would independently be of clinical value for disease staging, in concert with ECG, Echo and clinical assessments.


Assuntos
Cardiomiopatia Chagásica/sangue , Citocinas/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doadores de Sangue , Estudos de Casos e Controles , Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/terapia , Quimiocinas/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/sangue , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Estudos Retrospectivos , Trypanosoma cruzi/isolamento & purificação , Adulto Jovem
7.
Vox Sang ; 108(4): 350-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25678039

RESUMO

BACKGROUND AND OBJECTIVES: While the clinical impact of differences in red blood cell (RBC) component processing methods is unknown, there are concerns they may be confounding variables in studies such as the ongoing 'age of blood' investigations. Here, we compare the in vitro characteristics of red cell concentrates (RCCs) produced by several different processing methods. MATERIALS AND METHODS: Nine processing methods were examined: three apheresis methods (Alyx, MCS+ and Trima), as well as leucoreduced whole blood-derived RCCs produced by buffy coat and whole blood filtration and non-leucoreduced RCCs. RCCs were stored in saline-adenine-glucose-mannitol or additive solutions (AS) 1 or 3 for 42 days, with quality tested on day 5 and day 42. RESULTS: Many significant product differences were observed both early in and at the end of storage. Mean haemoglobin (Hb) ranged from 52 to 71 g/unit and mean Hct from 59·5 to 64·8%. Most RCC passed regulated quality control criteria according to Canadian Standards Association guidelines, although there were some failures relating to Hb content and residual WBC counts. CONCLUSION: Processing method impacts RCC characteristics throughout storage; better understanding of these differences and reporting of processing method details is critical.


Assuntos
Preservação de Sangue/métodos , Eritrócitos/química , Preservação de Sangue/normas , Hemoglobinas/análise , Humanos , Contagem de Leucócitos
8.
Eur J Heart Fail ; 17(4): 416-23, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25678239

RESUMO

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.


Assuntos
Cardiomiopatia Chagásica/sangue , DNA de Protozoário/sangue , Trypanosoma cruzi/genética , Adulto , Doadores de Sangue , Estudos de Casos e Controles , Cardiomiopatia Chagásica/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Trypanosoma cruzi/patogenicidade
9.
Vox Sang ; 107(4): 428-30, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25040346

RESUMO

Microchimerism (MC), the coexistence of allogeneic populations of cells within a host, is well described in pregnancy and blood transfusion. To date, transfusion-associated MC (TA-MC) appears unique to patients transfused after severe traumatic injury. We sought to determine whether transfusion in the peripartum period results in enduring, high-level TA-MC. We conducted a prospective cohort study of 22 women who were newly transfused within 48 h of delivery. Two subjects showed evidence of transient TA-MC; however, MC was not detected at 6 weeks and 6 months. The negative findings suggest that enduring TA-MC does not occur in this population.


Assuntos
Quimerismo , Reação Transfusional , Quimeras de Transplante/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Período Periparto , Gravidez , Estudos Prospectivos , Ferimentos e Lesões/terapia
10.
Vox Sang ; 107(4): 351-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24976130

RESUMO

BACKGROUND AND OBJECTIVES: Transfusion is associated with a risk of infection and alloimmunization. Pathogen reduction using riboflavin and UV light (Mirasol treatment) inactivates pathogens and leucocytes. With increasing adoption of the technology in clinical use, regulatory agencies have recommended the introduction of quality control measures to monitor pathogen reduction efficacy. We sought to develop a real-time PCR-based assay to document the impact of pathogen reduction on the mitochondrial genome in blood components. MATERIALS AND METHODS: DNA was extracted from platelet and plasma components before and after treatment with riboflavin and UV light. Inhibition of PCR amplification of mitochondrial DNA (mtDNA) in short- and long-amplicon target regions, ranging from under 200 base pairs (bp) to over 1800 bp, was measured in treated relative to untreated components. RESULTS: Pathogen reduction of platelets using riboflavin and UV light resulted in inhibition of PCR amplification of long-amplicon mtDNA targets, demonstrating approximately 1 log reduction of amplification relative to untreated products. Amplification of short-amplicon mtDNA targets was not affected by treatment. Evaluation of 110 blinded platelet samples from the PREPAReS clinical trial resulted in prediction of treatment status with 100% accuracy. Pathogen reduction of plasma components resulted in similar levels of PCR inhibition, while testing of 30 blinded plasma samples resulted in prediction of treatment status with 93% accuracy. CONCLUSION: A differential sized amplicon real-time PCR assay of mitochondrial DNA effectively documents nucleic acid damage induced by Mirasol treatment of platelets. The use of the assay for plasma product pathogen reduction requires further investigation.


Assuntos
Patógenos Transmitidos pelo Sangue/efeitos dos fármacos , Patógenos Transmitidos pelo Sangue/efeitos da radiação , DNA Mitocondrial/análise , Mitocôndrias/genética , Reação em Cadeia da Polimerase em Tempo Real , Riboflavina/farmacologia , Raios Ultravioleta , Plaquetas/metabolismo , Plaquetas/microbiologia , DNA Mitocondrial/normas , Humanos , Plasma/microbiologia , Controle de Qualidade , Reação em Cadeia da Polimerase em Tempo Real/normas
11.
Genes Immun ; 15(7): 500-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25030430

RESUMO

The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illumina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio=2.16, P=1.16E-07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 × 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.


Assuntos
Crioglobulinas/análise , Hepatite C/complicações , Polimorfismo de Nucleotídeo Único , Vasculite/genética , Estudos de Casos e Controles , Cromossomos Humanos Par 6/genética , Crioglobulinemia/etiologia , Crioglobulinemia/genética , Feminino , Genes MHC da Classe II , Estudo de Associação Genômica Ampla , Humanos , Masculino , Proteínas Proto-Oncogênicas/genética , Receptor Notch4 , Receptores Notch/genética , Vasculite/etiologia
12.
Epidemiol Infect ; 141(3): 591-5, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22640592

RESUMO

West Nile virus (WNV) was first recognized in the USA in 1999. We estimated the cumulative incidence of WNV infection in the USA from 1999 to 2010 using recently derived age- and sex-stratified ratios of infections to WNV neuroinvasive disease (WNND) and the number of WNND cases reported to national surveillance. We estimate that over 3 million persons have been infected with WNV in the USA, with the highest incidence rates in the central plains states. These 3 million infections would have resulted in about 780 000 illnesses. A substantial number of WNV infections and illnesses have occurred during the virus' first decade in the USA.


Assuntos
Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
15.
J Viral Hepat ; 17(3): 192-200, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19674288

RESUMO

Claudin-1 is a recently discovered co-receptor for hepatitis C virus (HCV) that is required for late-stage binding of the virus. Because variants in the gene that encodes claudin-1 (CLDN1) could play a role in HCV infection, we conducted a 'whole gene association study' among injection drug users (IDUs) to examine whether CLDN1 genetic variants were associated with the risk of HCV infection or with viral clearance. In a cross sectional study, we examined genotype results for 50 single nucleotide polymorphisms (SNPs) across the CLDN1 gene region, comparing genotypes among participants with chronic HCV (n = 658) to those in IDUs who had cleared HCV (n = 199) or remained HCV-uninfected (n = 68). Analyses were controlled for racial ancestry (African-American or European-American) by stratification and logistic regression modeling. We found that participants who remained uninfected more often carried CLDN1 promoter region SNPs -15312C [odds ratio (OR), 1.72; 95% confidence interval (CI) 1.00-2.94; P = 0.048], -7153A (OR, 2.13; 95% CI, 1.25-3.62; P = 0.006) and -5414C (OR, 1.78; 95% CI, 1.06-3.00; P = 0.03). HCV-uninfected participants less often carried CLDN1 IVS1-2983C (OR, 0.55; 95% CI, 0.31-0.97; P = 0.04), which lies in intron 1. CLDN1 -15312C, -7153A and -5414C formed a haplotype in both the African-American and European-American participants and a haplotype analysis supported the association of CLDN1 -7153A in the HCV-uninfected participants. The analyses of HCV clearance revealed no associations with any SNP. These results indicate that genetic variants in regulatory regions of CLDN1 may alter susceptibility to HCV infection.


Assuntos
Predisposição Genética para Doença , Hepatite C/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Adulto , Claudina-1 , Estudos Transversais , Usuários de Drogas , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa
16.
Vox Sang ; 98(4): 495-503, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19951309

RESUMO

There exists considerable risk for transfusion transmission of arboviruses due to short periods of asymptomatic viraemia in populations with variable and sometimes extremely high incidence of arboviral infections. Aside from West Nile virus, few arbovirus transfusion transmissions have been proven, mostly due to difficulties in ruling out vector-borne transmission in recipients with arbovirus disease. Nevertheless, arbovirus transfusion risk models and assessments of viraemia prevalence in blood donations indicate substantial transfusion transmission of dengue and Chikungunya viruses in epidemic areas. Many other arboviruses, several of which are importation risks in the Americas, Europe and Asia, also cause large outbreaks and threaten transfusion safety. Prevention largely depends on excluding donors from outbreak areas or implementation of highly sensitive nucleic acid amplification tests. Because of the increasing emergence of arboviral disease globally, it is prudent to prepare for both endemic and exotic arboviruses capable of producing large epidemics and subsequent transfusion transmission risk.


Assuntos
Infecções por Arbovirus/transmissão , Reação Transfusional , Viremia/transmissão , Infecções por Arbovirus/sangue , Humanos , Fatores de Risco , Viremia/sangue
17.
J Viral Hepat ; 16(1): 10-20, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18647233

RESUMO

T-cell responses to hepatitis C virus (HCV) antigens have been reported in high-risk HCV seronegative persons, suggesting that an effective cellular immune response might be able to clear infection without the development of antibodies. Such findings, however, could be explained by waning antibody or cross-reactivity to other antigens. To address these issues, we evaluated HCV-specific T-cell responses in 26 young (age 18-33 years) aviremic, seronegative injection drug users (IDUs) (median duration of injection, 6 years) by interferon-gamma enzyme-linked immunospot (ELISpot) assay using 429 overlapping HCV peptides pooled in 21 mixes. Seventeen aviremic, seropositive IDUs (spontaneous resolvers) and 15 healthy people were used as positive and negative controls, respectively. The percentage of patients with HCV-specific cellular immune responses was similar in seronegative and seropositive aviremic IDUs (46%vs 59%, P = 0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, six (23%) had intermediate to very strong responses to 10-20 peptide mixes and another six (23%) had moderately strong responses for two to six mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographical and behavioural risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs 0.26, P < 0.01). In conclusion, HCV-specific T-cell responses are common among high-risk, seronegative IDUs. The responses are broad and are associated with risk factors for HCV exposure, suggesting that they reflect true exposure to HCV in seronegative persons.


Assuntos
Usuários de Drogas , Anticorpos Anti-Hepatite C/sangue , Hepatite C/imunologia , Abuso de Substâncias por Via Intravenosa/complicações , Linfócitos T/imunologia , Adulto , Antígenos Virais/imunologia , Feminino , Humanos , Interferon gama/metabolismo , Masculino , Adulto Jovem
18.
J Viral Hepat ; 15(9): 690-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18507757

RESUMO

Infection with hepatitis C virus (HCV) may suppress co-infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross-sectional study during 1998-2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18-29 years to 1.03% in those >or=50 years old (P(trend) = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P < 0.0001), but this inverse relationship was much stronger in the oldest (>50 years; OR = 0.15) than the youngest (18-29 years; OR = 0.81) participants (P(trend) = 0.03). Similar results were obtained when duration of injection drug use was substituted for age (P(trend) = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co-infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections.


Assuntos
Hepatite B/epidemiologia , Hepatite C Crônica/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Adolescente , Adulto , Fatores Etários , Criança , Estudos Transversais , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas , RNA Viral/sangue
19.
J Viral Hepat ; 15(2): 120-8, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18184195

RESUMO

Knowing the likely distribution of intervals from hepatitis C infection to first RNA-negativity is important in deciding about therapeutic intervention. Prospectively collected sera and data from the Transfusion-transmitted Viruses Study (1974-1980) provide specific dates of infection and pattern of alanine aminotransferase (ALT) elevations. We examined frequency, timing and correlates of spontaneous resolution for 94 acutely infected transfusion recipients followed for a median of 9.5 months. Later, follow-up sera (>10 years) were available for 27 of the 94 cases from a Veterans Administration (VA) Study (1989-1990). Twenty-five (27%) of the 94 cases were classified as probably resolved during the episode itself. First RNA negativity occurred at 6-50 weeks (median, 19.5 weeks) after infection, and 5-43 weeks (median, 11 weeks) after ALT elevation. Thirteen of the 25 cases remained RNA-negative subsequently; 12 others had 1-6 RNA-positive sera intercalated between first and last RNA-negative results. RNA negativity, therefore, began variably and was interrupted in 12 cases of 25 (48%) by transient RNA-positive sera. Five of these 25 patients who were RNA-negative in the last study specimen had late, Veterans Administration Study follow-up; none showed viraemia. Of the remaining 69 transfusion transmitted virus study recipients, whose last serum was RNA-positive, two cleared viraemia after the last study serum but before late follow-up. Eleven (16%) had 23 intercalated RNA-negative sera before last positivity. RNA status, therefore, needs monitoring for many months before judging the spontaneous outcome as transient negativity may occur. Resolution was significantly more common in women and symptomatic cases; it was not associated with viral load in the infectious donation, HCV genotype, or the recipient's age.


Assuntos
Hepacivirus/imunologia , Hepatite C/imunologia , Reação Transfusional , Viremia , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Doadores de Sangue , Hepacivirus/efeitos dos fármacos , Hepatite C/microbiologia , Hepatite C/fisiopatologia , Hepatite C/transmissão , Humanos , Estudos Prospectivos , RNA Viral/sangue , Carga Viral
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