ORCID Profile
0000-0002-2406-4426
Current Organisation
Imperial College London
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Publisher: Elsevier BV
Date: 06-2018
Publisher: Springer Science and Business Media LLC
Date: 15-01-2021
Publisher: Springer Science and Business Media LLC
Date: 25-12-2202
Publisher: Wiley
Date: 15-09-2016
DOI: 10.1111/APT.13779
Abstract: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w) TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w) TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P 3.5 log HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1053/J.GASTRO.2015.09.043
Abstract: Patients chronically infected with the hepatitis B virus rarely achieve loss of serum hepatitis B surface antigen (HBsAg) with the standard of care. We evaluated HBsAg loss in patients receiving the combination of tenofovir disoproxil fumarate (TDF) and peginterferon α-2a (peginterferon) for a finite duration in a randomized trial. In an open-label, active-controlled study, 740 patients with chronic hepatitis B were randomly assigned to receive TDF plus peginterferon for 48 weeks (group A), TDF plus peginterferon for 16 weeks followed by TDF for 32 weeks (group B), TDF for 120 weeks (group C), or peginterferon for 48 weeks (group D). The primary end point was the proportion of patients with serum HBsAg loss at week 72. At week seventy-two, 9.1% of subjects in group A had HBsAg loss compared with 2.8% of subjects in group B, none of the subjects in group C, and 2.8% of subjects in group D. A significantly higher proportion of subjects in group A had HBsAg loss than in group C (P < .001) or group D (P = .003). However, the proportions of subjects with HBsAg loss did not differ significantly between group B and group C (P = .466) or group D (P = .883). HBsAg loss in group A occurred in hepatitis B e antigen-positive and hepatitis B e antigen-negative patients with all major viral genotypes. The incidence of common adverse events (including headache, alopecia, and pyrexia) and treatment discontinuation due to adverse events was similar among groups. A significantly greater proportion of patients receiving TDF plus peginterferon for 48 weeks had HBsAg loss than those receiving TDF or peginterferon alone. ClinicalTrials.gov ID NCT01277601.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-01-2015
Abstract: Control of mosquito vectors has historically proven to be an effective means of eliminating malaria. Human malaria is transmitted only by mosquitoes in the genus Anopheles , but not all species within the genus, or even all members of each vector species, are efficient malaria vectors. Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. This variation in vectorial capacity suggests an underlying genetic/genomic plasticity that results in variation of key traits determining vectorial capacity within the genus. Sequencing the genome of Anopheles gambiae , the most important malaria vector in sub-Saharan Africa, has offered numerous insights into how that species became highly specialized to live among and feed upon humans and how susceptibility to mosquito control strategies is determined. Until very recently, similar genomic resources have not existed for other anophelines, limiting comparisons to in idual genes or sets of genomic markers with no genome-wide data to investigate attributes associated with vectorial capacity across the genus. We sequenced and assembled the genomes and transcriptomes of 16 anophelines from Africa, Asia, Europe, and Latin America, spanning ~100 million years of evolution and chosen to represent a range of evolutionary distances from An. gambiae , a variety of geographic locations and ecological conditions, and varying degrees of vectorial capacity. Genome assembly quality reflected DNA template quality and homozygosity. Despite variation in contiguity, the assemblies were remarkably complete and searches for arthropod-wide single-copy orthologs generally revealed few missing genes. Genome annotation supported with RNA sequencing transcriptomes yielded between 10,738 and 16,149 protein-coding genes for each species. Relative to Drosophila, the closest dipteran genus for which equivalent genomic resources exist, Anopheles exhibits a dynamic genomic evolutionary profile. Comparative analyses show a fivefold faster rate of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses in Anopheles . Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead ersify through protein-sequence changes. We also document evidence of variation in important reproductive phenotypes, genes controlling immunity to Plasmodium malaria parasites and other microbes, genes encoding cuticular and salivary proteins, and genes conferring metabolic insecticide resistance. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts. Anopheline mosquitoes exhibit a molecular evolutionary profile very distinct from Drosophila , and their genomes harbor strong evidence of functional variation in traits that determine vectorial capacity. These 16 new reference genome assemblies provide a foundation for hypothesis generation and testing to further our understanding of the erse biological traits that determine vectorial capacity. The maximum likelihood molecular phylogeny of all sequenced anophelines and two mosquito outgroups was constructed from the aligned protein sequences of 1085 single-copy orthologs. Shapes between branch termini and species names indicate vector status and are colored according to geographic ranges depicted on the map.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Andrea Crisanti.