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RISS 인기검색어
- 검색키워드
- 저자 : Katzelnick, Leah C. (검색결과 4 건)
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Immune correlates of protection for dengue: State of the art and research agenda
Katzelnick, Leah C.,Harris, Eva,Baric, Ralph,Coller, Beth-Ann,Coloma, Josefina,Crowe Jr., James E.,Cummings Jr., Derek A.T.,Dean Jr., Hansi,de Silva Jr., Aravinda,Diamond Jr., Michael S.,Durbin Jr., A Elsevier 2017 Vaccine Vol.35 No.36
<P><B>Abstract</B></P> <P>Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the “<I>Summit on Dengue Immune Correlates of Protection</I>”, held in Annecy, France, on March 8–9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.</P>
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Corbett, Kizzmekia S.,Katzelnick, Leah,Tissera, Hasitha,Amerasinghe, Ananda,de Silva, Aruna Dharshan,de Silva, Aravinda M. Oxford University Press 2015 The Journal of infectious diseases Vol.211 No.4
<P>Dengue viruses (DENVs) are mosquito-borne flaviviruses that infect humans. The clinical presentation of DENV infection ranges from inapparent infection to dengue hemorrhagic fever and dengue shock syndrome. We analyzed samples from a pediatric dengue cohort study in Sri Lanka to explore whether antibody responses differentiated clinically apparent infections from clinically inapparent infections. In DENV-naive individuals exposed to primary DENV infections, we observed no difference in the quantity or quality of acquired antibodies between inapparent and apparent infections. Children who experienced primary infections had broad, serotype–cross-neutralizing antibody responses that narrowed in breadth to a single serotype over a 12-month period after infection. In DENV immune children who were experiencing a repeat infection, we observed a strong association between preexisting neutralizing antibodies and clinical outcome. Notably, children with preexisting monospecific neutralizing antibody responses were more likely to develop fever than children with cross-neutralizing responses. Preexisting DENV neutralizing antibodies are correlated with protection from dengue disease.</P>
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Reconstruction of antibody dynamics and infection histories to evaluate dengue risk
Salje, Henrik,Cummings, Derek A. T.,Rodriguez-Barraquer, Isabel,Katzelnick, Leah C.,Lessler, Justin,Klungthong, Chonticha,Thaisomboonsuk, Butsaya,Nisalak, Ananda,Weg, Alden,Ellison, Damon,Macareo, Lou Nature Publishing Group UK 2018 Nature Vol.557 No.7707
<P>As with many pathogens, most dengue infections are subclinical and therefore unobserved(1). Coupled with limited understanding of the dynamic behaviour of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual-and population-level correlates of infection and disease risk and how these change over time, between assay interpretations and with cohort design. Here we develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 haemagglutination inhibition assay titre measurements)(2,3). We identify 1,149 infections (95% confidence interval, 1,135-1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. After infection, individuals develop a stable set point antibody load after one year that places them within or outside a risk window. Individuals with pre-existing titres of <= 1: 40 develop haemorrhagic fever 7.4 (95% confidence interval, 2.5-8.2) times more often than naive individuals compared to 0.0 times for individuals with titres > 1: 40 (95% confidence interval: 0.0-1.3). Plaque reduction neutralization test titres <= 1: 100 were similarly associated with severe disease. Across the population, variability in the size of epidemics results in large-scale temporal changes in infection and disease risk that correlate poorly with age.</P>
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Burden of dengue infection and disease in a pediatric cohort in urban Sri Lanka.
Tissera, Hasitha,Amarasinghe, Ananda,De Silva, Aruna Dharshan,Kariyawasam, Pradeep,Corbett, Kizzmekia S,Katzelnick, Leah,Tam, Clarence,Letson, G William,Margolis, Harold S,de Silva, Aravinda M Allen Press, etc.] 2014 The American journal of tropical medicine and hygi Vol.91 No.1
<P>Dengue is the most significant arthropod-borne viral infection of humans. Persons infected with dengue viruses (DENV) have subclinical or clinically apparent infections ranging from undifferentiated fever to dengue hemorrhagic fever/shock syndrome. Although recent studies estimated that the Indian subcontinent has the greatest burden of DENV infection and disease worldwide, we do not have reliable, population-based estimates of the incidence of infection and disease in this region. The goal of this study was to follow-up a cohort of 800 children living in a heavily urbanized area of Colombo, Sri Lanka to obtain accurate estimates of the incidence of DENV infection and disease. Annual blood samples were obtained from all children to estimate dengue seroprevalence at enrollment and to identify children exposed to new DENV infections during the study year. Blood was also obtained from any child in whom fever developed over the course of the study year to identify clinically apparent DENV infections. At enrollment, dengue seroprevalence was 53.07%, which indicated high transmission in this population. Over the study year, the incidence of DENV infection and disease were 8.39 (95% confidence interval = 6.56-10.53) and 3.38 (95% confidence interval = 2.24-4.88), respectively, per 100 children per year. The ratio of clinically inapparent to apparent infections was 1.48. These results will be useful for obtaining more accurate estimates of the burden of dengue in the region and for making decisions about testing and introduction of vaccines.</P>
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