Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Mais filtros

Bases de dados
Tipo de documento
Intervalo de ano de publicação
1.
Mol Biol Evol ; 39(3)2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35106603

RESUMO

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.


Assuntos
COVID-19 , SARS-CoV-2 , Hospitais , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2/genética
2.
BMC Infect Dis ; 23(1): 446, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400776

RESUMO

BACKGROUND: Due to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine. METHODS: In this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships. RESULTS: Between June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement. CONCLUSIONS: Locally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.


Assuntos
Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Hepacivirus/genética , Ucrânia/epidemiologia , Estudos Transversais , Filogenia , Estudos Soroepidemiológicos , Teorema de Bayes , Infecções por HIV/complicações , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Prevalência
3.
J Infect Dis ; 226(12): 2142-2149, 2022 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-35771664

RESUMO

BACKGROUND: Monitoring the emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is an important public health objective. We investigated how the Gamma variant was established in New York City (NYC) in early 2021 in the presence of travel restrictions that aimed to prevent viral spread from Brazil, the country where the variant was first identified. METHODS: We performed phylogeographic analysis on 15 967 Gamma sequences sampled between 10 March and 1 May 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. RESULTS: We identified 16 phylogenetically distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes); most of them were introduced from Florida and Illinois and only 1 directly from Brazil. By the time the first Gamma case was reported by genomic surveillance in NYC on 10 March, the majority (57%) of circulating Gamma lineages had already been established in the city for at least 2 weeks. CONCLUSIONS: Although travel from Brazil to the United States was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Cidade de Nova Iorque/epidemiologia , COVID-19/epidemiologia , Filogenia
4.
Eur J Public Health ; 31(1): 63-67, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32951027

RESUMO

BACKGROUND: There are over 1 million people living with HIV in Russia, and less than half of them are on antiretroviral treatment (ART). Earlier in the epidemic, Russia was successful in implementing prevention of mother-to-child transmission programmes; however, there is a gap in knowledge about postpartum adherence to ART among women living with HIV (WLHIV). The objective of our research study was to identify which factors are associated with postpartum engagement in HIV care and treatment in Russia. METHODS: We conducted a community-based participatory research study in five Russian cities. We surveyed 200 WLHIV who had given birth within the previous 24 months about their use of ART. We used multivariable logistic regression to determine which types of social support are associated with adherence to ART in the postpartum period. RESULTS: Less than half (40%) of mothers reported being adherent to ART. Multivariable analysis showed that having a supportive family environment [aOR = 2.64, 95% CI (1.91-5.83)], and active engagement with other HIV-positive mothers [aOR = 2.20, 95% CI (1.04-4.66)] were positively associated with postpartum adherence to ART. WLHIV who had more than one child were less likely to be adherent then WLHIV with just one child [aOR = 0.44, 95% CI (0.22-0.91)]. CONCLUSION: The support that new mothers have or do not have can play an important role in WLHIV adherence to ART. The findings from our study provide ideas for improving the likelihood that women will continue to engage in HIV treatment and care after pregnancy.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Fármacos Anti-HIV/uso terapêutico , Criança , Pesquisa Participativa Baseada na Comunidade , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Adesão à Medicação , Período Pós-Parto , Gravidez , Federação Russa , Apoio Social
5.
J Virol ; 90(21): 9683-9692, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27535047

RESUMO

RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among the human population, and their ability to evolve resistance to antiviral therapies. The recent emergence of chikungunya virus, Zika virus, and Ebola virus highlights the struggles to contain outbreaks. A significant hurdle is the availability of antivirals to treat the infected or protect at-risk populations. While several compounds show promise in vitro and in vivo, these outbreaks underscore the need to accelerate drug discovery. The replication of several viruses has been described to rely on host polyamines, small and abundant positively charged molecules found in the cell. Here, we describe the antiviral effects of two molecules that alter polyamine levels: difluoromethylornithine (DFMO; also called eflornithine), which is a suicide inhibitor of ornithine decarboxylase 1 (ODC1), and diethylnorspermine (DENSpm), an activator of spermidine/spermine N1-acetyltransferase (SAT1). We show that reducing polyamine levels has a negative effect on diverse RNA viruses, including several viruses involved in recent outbreaks, in vitro and in vivo These findings highlight the importance of the polyamine biosynthetic pathway to viral replication, as well as its potential as a target in the development of further antivirals or currently available molecules, such as DFMO. IMPORTANCE: RNA viruses present a significant hazard to human health, and combatting these viruses requires the exploration of new avenues for targeting viral replication. Polyamines, small positively charged molecules within the cell, have been demonstrated to facilitate infection for a few different viruses. Our study demonstrates that diverse RNA viruses rely on the polyamine pathway for replication and highlights polyamine biosynthesis as a promising drug target.


Assuntos
Antivirais/farmacologia , Poliaminas/metabolismo , Vírus de RNA/efeitos dos fármacos , Acetiltransferases/metabolismo , Animais , Linhagem Celular , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/virologia , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/metabolismo , Surtos de Doenças , Ebolavirus/efeitos dos fármacos , Ebolavirus/metabolismo , Eflornitina/farmacologia , Doença pelo Vírus Ebola/tratamento farmacológico , Doença pelo Vírus Ebola/virologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Espermina/análogos & derivados , Espermina/farmacologia , Replicação Viral/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/virologia
6.
J Clin Microbiol ; 52(11): 3913-21, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25143582

RESUMO

In critically ill patients, the development of pneumonia results in significant morbidity and mortality and additional health care costs. The accurate and rapid identification of the microbial pathogens in patients with pulmonary infections might lead to targeted antimicrobial therapy with potentially fewer adverse effects and lower costs. Major advances in next-generation sequencing (NGS) allow culture-independent identification of pathogens. The present study used NGS of essentially full-length PCR-amplified 16S ribosomal DNA from the bronchial aspirates of intubated patients with suspected pneumonia. The results from 61 patients demonstrated that sufficient DNA was obtained from 72% of samples, 44% of which (27 samples) yielded PCR amplimers suitable for NGS. Out of the 27 sequenced samples, only 20 had bacterial culture growth, while the microbiological and NGS identification of bacteria coincided in 17 (85%) of these samples. Despite the lack of bacterial growth in 7 samples that yielded amplimers and were sequenced, the NGS identified a number of bacterial species in these samples. Overall, a significant diversity of bacterial species was identified from the same genus as the predominant cultured pathogens. The numbers of NGS-identifiable bacterial genera were consistently higher than identified by standard microbiological methods. As technical advances reduce the processing and sequencing times, NGS-based methods will ultimately be able to provide clinicians with rapid, precise, culture-independent identification of bacterial, fungal, and viral pathogens and their antimicrobial sensitivity profiles.


Assuntos
Bactérias/classificação , Bactérias/genética , Pulmão/microbiologia , Microbiota , Pneumonia Associada à Ventilação Mecânica/microbiologia , Idoso , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
7.
PNAS Nexus ; 2(3): pgad008, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36896134

RESUMO

Internally displaced persons are often excluded from HIV molecular epidemiology surveillance due to structural, behavioral, and social barriers in access to treatment. We test a field-based molecular epidemiology framework to study HIV transmission dynamics in a hard-to-reach and highly stigmatized group, internally displaced people who inject drugs (IDPWIDs). We inform the framework by Nanopore generated HIV pol sequences and IDPWID migration history. In June-September 2020, we recruited 164 IDPWID in Odesa, Ukraine, and obtained 34 HIV sequences from HIV-infected participants. We aligned them to publicly available sequences (N = 359) from Odesa and IDPWID regions of origin and identified 7 phylogenetic clusters with at least 1 IDPWID. Using times to the most recent common ancestors of the identified clusters and times of IDPWID relocation to Odesa, we infer potential post-displacement transmission window when infections likely to happen to be between 10 and 21 months, not exceeding 4 years. Phylogeographic analysis of the sequence data shows that local people in Odesa disproportionally transmit HIV to the IDPWID community. Rapid transmissions post-displacement in the IDPWID community might be associated with slow progression along the HIV continuum of care: only 63% of IDPWID were aware of their status, 40% of those were in antiviral treatment, and 43% of those were virally suppressed. Such HIV molecular epidemiology investigations are feasible in transient and hard-to-reach communities and can help indicate best times for HIV preventive interventions. Our findings highlight the need to rapidly integrate Ukrainian IDPWID into prevention and treatment services following the dramatic escalation of the war in 2022.

8.
Materials (Basel) ; 15(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35057137

RESUMO

The purpose of this research was to analyze the change in residual stresses in the surface layer of steel samples taking into account the technological heredity effect on the value and sign of residual stresses. An installation of combined processing was developed. Combined processing consists of sequentially performing electromechanical processing and diamond smoothing. All areas of the samples were studied-after machining (i.e., in the initial state), after electromechanical processing, and after diamond smoothing. The research shows that the sign and value of residual stresses are significantly affected by the combined processing modes. The main parameters of the surface layer are formed at the final stage of the combined processing-diamond smoothing. This paper gives recommendations on the use of combined processing for power plant parts.

9.
Sci Rep ; 12(1): 15749, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131001

RESUMO

The use of real-time genomic epidemiology has enabled the tracking of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), informing evidence-based public health decision making. Ukraine has experienced four waves of the Coronavirus Disease 2019 (COVID-19) between spring 2020 and spring 2022. However, insufficient capacity for local genetic sequencing limited the potential application of SARS-CoV-2 genomic surveillance for public health response in the country. Herein, we report local sequencing of 103 SARS-CoV-2 genomes from patient samples collected in Kyiv in July-December 2021 using Oxford Nanopore technology. Together with other published Ukrainian SARS-CoV-2 genomes, our data suggest that the third wave of the epidemic in Ukraine (June-December 2021) was dominated by the Delta Variant of Concern (VOC). Our phylogeographic analysis revealed that in summer 2021 Delta VOC was introduced into Ukraine from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. The wide geographic range of Delta introductions coincides with increased volume of travel to Ukraine particularly from locations outside of Europe in summer 2021. This study highlights the need to urgently integrate affordable and easily scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.


Assuntos
COVID-19 , Sequenciamento por Nanoporos , COVID-19/epidemiologia , Humanos , SARS-CoV-2/genética , Ucrânia/epidemiologia
10.
Res Sq ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34873595

RESUMO

Since spring 2020, Ukraine has experienced at least two COVID-19 waves and has just entered a third wave in autumn 2021. The use of real-time genomic epidemiology has enabled the tracking of SARS-CoV-2 circulation patterns worldwide, thus informing evidence-based public health decision making, including implementation of travel restrictions and vaccine rollout strategies. However, insufficient capacity for local genetic sequencing in Ukraine and other Lower and Middle-Income countries limit opportunities for similar analyses. Herein, we report local sequencing of 24 SARS-CoV-2 genomes from patient samples collected in Kyiv in July 2021 using Oxford Nanopore MinION technology. Together with other published Ukrainian SARS-COV-2 genomes sequenced mostly abroad, our data suggest that the second wave of the epidemic in Ukraine (February-April 2021) was dominated by the Alpha variant of concern (VOC), while the beginning of the third wave has been dominated by the Delta VOC. Furthermore, our phylogeographic analysis revealed that the Delta variant was introduced into Ukraine in summer 2021 from multiple locations worldwide, with most introductions coming from Central and Eastern European countries. This study highlights the need to urgently integrate affordable and easily-scaled pathogen sequencing technologies in locations with less developed genomic infrastructure, in order to support local public health decision making.

11.
Elife ; 102021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387545

RESUMO

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95.1% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within- and between-host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.


The COVID-19 pandemic has had major health impacts across the globe. The scientific community has focused much attention on finding ways to monitor how the virus responsible for the pandemic, SARS-CoV-2, spreads. One option is to perform genetic tests, known as sequencing, on SARS-CoV-2 samples to determine the genetic code of the virus and to find any differences or mutations in the genes between the viral samples. Viruses mutate within their hosts and can develop into variants that are able to more easily transmit between hosts. Genetic sequencing can reveal how genetically similar two SARS-CoV-2 samples are. But tracking how SARS-CoV-2 moves from one person to the next through sequencing can be tricky. Even a sample of SARS-CoV-2 viruses from the same individual can display differences in their genetic material or within-host variants. Could genetic testing of within-host variants shed light on factors driving SARS-CoV-2 to evolve in humans? To get to the bottom of this, Tonkin-Hill, Martincorena et al. probed the genetics of SARS-CoV-2 within-host variants using 1,181 samples. The analyses revealed that 95.1% of samples contained within-host variants. A number of variants occurred frequently in many samples, which were consistent with mutational hotspots in the SARS-CoV-2 genome. In addition, within-host variants displayed mutation patterns that were similar to patterns found between infected individuals. The shared within-host variants between samples can help to reconstruct transmission chains. However, the observed mutational hotspots and the detection of multiple strains within an individual can make this challenging. These findings could be used to help predict how SARS-CoV-2 evolves in response to interventions such as vaccines. They also suggest that caution is needed when using information on within-host variants to determine transmission between individuals.


Assuntos
COVID-19/genética , COVID-19/fisiopatologia , Variação Genética , Genoma Viral , Interações Hospedeiro-Patógeno/genética , Mutação , SARS-CoV-2/genética , Sequência de Bases , Humanos , Pandemias , Filogenia
12.
Elife ; 102021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34425938

RESUMO

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.


The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a global public health challenge. Hospitals have been at the forefront of this battle, treating large numbers of sick patients over several waves of infection. Finding ways to manage the spread of the virus in hospitals is key to protecting vulnerable patients and workers, while keeping hospitals running, but to generate effective infection control, researchers must understand how SARS-CoV-2 spreads. A range of factors make studying the transmission of SARS-CoV-2 in hospitals tricky. For instance, some people do not present any symptoms, and, amongst those who do, it can be difficult to determine whether they caught the virus in the hospital or somewhere else. However, comparing the genetic information of the SARS-CoV-2 virus from different people in a hospital could allow scientists to understand how it spreads. Samples of the genetic material of SARS-CoV-2 can be obtained by swabbing infected individuals. If the genetic sequences of two samples are very different, it is unlikely that the individuals who provided the samples transmitted the virus to one another. Illingworth, Hamilton et al. used this information, along with other data about how SARS-CoV-2 is transmitted, to develop an algorithm that can determine how the virus spreads from person to person in different hospital wards. To build their algorithm, Illingworth, Hamilton et al. collected SARS-CoV-2 genetic data from patients and staff in a hospital, and combined it with information about how SARS-CoV-2 spreads and how these people moved in the hospital . The algorithm showed that, for the most part, patients were infected by other patients (20 out of 22 cases), while staff were infected equally by patients and staff. By further probing these data, Illingworth, Hamilton et al. revealed that 80% of hospital-acquired infections were caused by a group of just 21% of individuals in the study, identifying a 'superspreader' pattern. These findings may help to inform SARS-CoV-2 infection control measures to reduce spread within hospitals, and could potentially be used to improve infection control in other contexts.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Surtos de Doenças/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Elife ; 102021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650490

RESUMO

COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1167 residents from 337 care homes were identified from a dataset of 6600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.


Assuntos
COVID-19/epidemiologia , COVID-19/transmissão , Casas de Saúde , SARS-CoV-2/genética , Idoso de 80 Anos ou mais , COVID-19/virologia , Surtos de Doenças , Inglaterra/epidemiologia , Feminino , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Transmissão de Doença Infecciosa do Profissional para o Paciente , Masculino , Polimorfismo de Nucleotídeo Único , Análise de Sequência , Fatores de Tempo
14.
Semin Arthritis Rheum ; 50(1): 149-155, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31303436

RESUMO

OBJECTIVE: Juvenile idiopathic inflammatory myopathies (JIIM) are rare, chronic autoimmune muscle diseases of childhood, with the potential for significant morbidity. Data on long-term outcomes is limited. In this study we investigate correlations between clinical and demographic features with long-term outcomes in a referral population of adult patients with JIIM. METHODS: Forty-nine adults with JIIM were assessed at two referral centers between 1994 and 2016. Features of active disease and damage at a cross-sectional assessment were obtained. Regression modeling was used to examine factors associated with long-term outcomes, defined by the presence of calcinosis or a higher adjusted Myositis Damage Index (MDI) score. A multivariable model of MDI was constructed using factors that were statistically significant in bivariate models. RESULTS: At a median of 11.5 [IQR 4.5-18.9] years following diagnosis, median American College of Rheumatology (ACR) functional class was 2 [1.5-3.0], Health Assessment Questionnaire (HAQ) score was 0.4 out of 3.0 [0.0-1.0], and manual muscle testing (MMT) score was 229 out of 260 [212.6-256.8]. Median MDI score was 6.0 [3.5-8.9], with the most commonly damaged organ systems being cutaneous and musculoskeletal. Factors associated with an elevated MDI score were the presence of erythroderma and other cutaneous manifestations, disease duration, and ACR functional class. Calcinosis was present in 55% of patients. The strongest predictors of calcinosis were disease duration, periungual capillary changes, and younger age at diagnosis. CONCLUSION: In a tertiary referral population, long-term functional outcomes of JIIM are generally favorable, with HAQ scores indicative of mild disability. Although most patients had mild disease activity and virtually all had significant disease damage, severe or systemic damage was rare. Certain clinical features are associated with long-term damage and calcinosis.


Assuntos
Calcinose/complicações , Dermatomiosite/diagnóstico , Pele/fisiopatologia , Adolescente , Adulto , Calcinose/fisiopatologia , Dermatomiosite/complicações , Dermatomiosite/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
Lancet Infect Dis ; 20(11): 1263-1272, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32679081

RESUMO

BACKGROUND: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. METHODS: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. FINDINGS: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. INTERPRETATION: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. FUNDING: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Infecção Hospitalar/virologia , Inglaterra/epidemiologia , Feminino , Genoma Viral/genética , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Filogenia , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , SARS-CoV-2 , Sequenciamento Completo do Genoma/métodos , Adulto Jovem
17.
Nat Commun ; 11(1): 6385, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318491

RESUMO

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Imunidade Humoral/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/uso terapêutico , Antivirais/uso terapêutico , COVID-19/virologia , Febre/prevenção & controle , Humanos , Imunidade Humoral/imunologia , Contagem de Linfócitos , Masculino , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Resultado do Tratamento
18.
Genome Biol ; 20(1): 1, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606230

RESUMO

The Network of Cancer Genes (NCG) is a manually curated repository of 2372 genes whose somatic modifications have known or predicted cancer driver roles. These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of more than 100 cancer types from 34,905 cancer donors and multiple primary sites. This represents a more than 1.5-fold content increase compared to the previous version. NCG also annotates properties of cancer genes, such as duplicability, evolutionary origin, RNA and protein expression, miRNA and protein interactions, and protein function and essentiality. NCG is accessible at http://ncg.kcl.ac.uk/ .


Assuntos
Bases de Dados Genéticas , Genes Neoplásicos , Heterogeneidade Genética , Humanos
20.
PLoS One ; 13(7): e0192598, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29985913

RESUMO

The diagnosis of strongyloidiasis by coprological methods has a low sensitivity, underestimating the prevalence of Strongyloides stercoralis in endemic areas. Serodiagnostic tests for strongyloidiasis have shown robust diagnostic properties. However, these methods require a blood draw, an invasive and labor-intensive sample collection method, especially in the resource-limited settings where S. stercoralis is endemic. Our study examines a urine-based assay for strongyloidiasis and compares its diagnostic accuracy with coprological and serological methods. Receiver operating characteristic (ROC) curve analyses determined the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the urine ELISA, as well as estimates its positive predictive value and diagnostic risk. The likelihood ratios of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for each diagnostic positivity threshold. The urine ELISA assay correlated significantly with the serological ELISA assay for strongyloidiasis, with a D-Sn of 92.7% and a D-Sp of 40.7%, when compared to coprological methods. Moreover, the urine ELISA IgG test had a detection rate of 69%, which far exceeds the coprological method (28%). The likelihood of a positive diagnosis of strongyloidiasis by the urine ELISA IgG test increased significantly with increasing units of IgG detected in urine. The urine ELISA IgG assay for strongyloidiasis assay has a diagnostic accuracy comparable to serological assay, both of which are more sensitive than coprological methods. Since the collection of urine is easy and non-invasive, the urine ELISA IgG assay for strongyloidiasis could be used to screen populations at risk for strongyloidiasis in S. stercoralis endemic areas.


Assuntos
Anticorpos Anti-Helmínticos/urina , Antígenos de Helmintos/imunologia , Doenças Endêmicas , Imunoglobulina G/urina , Strongyloides stercoralis/imunologia , Estrongiloidíase/diagnóstico , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Fezes/parasitologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/sangue , Estrongiloidíase/epidemiologia , Estrongiloidíase/urina , Tailândia/epidemiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA