Human to Mosquito Transmission of Dengue Viruses

The successful transmission of dengue virus from a human host to a mosquito vector requires a complex set of factors to align. It is becoming increasingly important to improve our understanding of the parameters that shape the human to mosquito component of the transmission cycle so that vaccines and therapeutic antivirals can be fully evaluated and epidemiological models refined. Here we describe these factors, and discuss the biological and environmental impacts and demographic changes that are influencing these dynamics. Specifically, we examine features of the human infection required for the mosquito to acquire the virus via natural blood feeding, as well as the biological and environmental factors that influence a mosquito's susceptibility to infection, up to the point that they are capable of transmitting the virus to a new host

Investing in California’s Transportation Future: Public Opinion on Critical Needs

In 2017, the State of California adopted landmark legislation to increase the funds available for transportation in the state: Senate Bill 1 (SB1), the Road Repair and Accountability Act of 2017. Through a combination of higher gas and diesel motor fuel taxes, SB1 raises revenue for four critical transportation needs in the state: road maintenance and rehabilitation, relief from congestion, improvements to trade corridors, and improving transit and rail services. To help state leaders identify the most important projects and programs to fund within those four topical areas, we conducted an online survey that asked a sample of 3,574 adult Californians their thoughts on how the state can achieve the SB1 objectives. The survey was administered from April to August 2019 with a survey platform and panel of respondents managed by Qualtrics. Quota sampling ensured that the final sample closely reflects California adults in terms of key socio-demographic characteristics and geographic distribution. Key findings included very strong support for improving all transportation modes, reducing air pollution and greenhouse gas emissions from transportation, and more convenient options to travel without driving. Respondents placed particular value on better maintenance for both local streets and roads, as well as highways. Finally, the majority of respondents assessed all types of transportation infrastructure in their communities as somewhat or very good

Dengue human infection models supporting drug development.

Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue

Assessing dengue vaccination impact: Model challenges and future directions.

In response to the sharp rise in the global burden caused by dengue virus (DENV) over the last few decades, the WHO has set out three specific key objectives in its disease control strategy: (i) to estimate the true burden of dengue by 2015; (ii) a reduction in dengue mortality by at least 50% by 2020 (used as a baseline); and (iii) a reduction in dengue morbidity by at least 25% by 2020. Although various elements will all play crucial parts in achieving this goal, from diagnosis and case management to integrated surveillance and outbreak response, sustainable vector control, vaccine implementation and finally operational and implementation research, it seems clear that new tools (e.g. a safe and effective vaccine and/or effective vector control) are key to success. The first dengue vaccine was licensed in December 2015, Dengvaxia® (CYD-TDV) developed by Sanofi Pasteur. The WHO has provided guidance on the use of CYD-TDV in endemic countries, for which there are a variety of considerations beyond the risk-benefit evaluation done by regulatory authorities, including public health impact and cost-effectiveness. Population-level vaccine impact and economic and financial aspects are two issues that can potentially be considered by means of mathematical modelling, especially for new products for which empirical data are still lacking. In December 2014 a meeting was convened by the WHO in order to revisit the current status of dengue transmission models and their utility for public health decision-making. Here, we report on the main points of discussion and the conclusions of this meeting, as well as next steps for maximising the use of mathematical models for vaccine decision-making

Kinetics of Viremia and NS1 Antigenemia Are Shaped by Immune Status and Virus Serotype in Adults with Dengue

Dengue is an acute viral disease that affects tens of millions of people annually in tropical and sub-tropical countries. In some cases, this infection happens to be severe and even life threatening. Severe cases have been associated with higher levels of virus in the blood. Several hypotheses have been proposed to explain the occurrence of these cases notably by involving the patient's history of previous DEN virus infection(s). Little is known about the relationships between the evolution over time of virus levels in the blood, the clinical outcome and the previous infection(s) history—a better understanding of these features could help in anti-viral drug development. To analyze these relationships, we studied well characterized patients who participated in a clinical trial. The majority of these patients were infected by DENV-1 serotype and had higher levels of virus than those infected by DENV-2 and sometimes DENV-3 serotypes. We also found that patients with more severe symptoms had higher levels of virus in the first days of their illness. We found as well that the virus was cleared faster and earlier from the blood of patients previously infected. These findings are of major importance for further anti-viral drug testing

Evolutionarily Successful Asian 1 Dengue Virus 2 Lineages Contain One Substitution in Envelope That Increases Sensitivity to Polyclonal Antibody Neutralization.

This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/infdis/jiv536The 4 dengue virus serotypes (DENV-1-4) cause the most prevalent mosquito-borne viral disease of humans worldwide. DENV-2 Asian 1 (A1) genotype viruses replaced the Asian-American (AA) genotype in Vietnam and Cambodia, after which A1 viruses containing Q or M at envelope (E) residue 160 became more prevalent than those with residue 160K in both countries (2008-2011). We investigated whether these substitutions conferred a fitness advantage by measuring neutralizing antibody titer against reporter virus particles (RVPs) representing AA, A1-160K, A1-160Q, and A1-160M, using patient sera from Vietnam and a well-characterized Nicaraguan cohort. Surprisingly, we found that A1-160Q and A1-160M RVPs were better neutralized by heterologous antisera than A1-160K. Despite this, Vietnamese patients infected with A1-160Q or A1-160M viruses had higher viremia levels than those infected with A1-160K. We thus found that independent lineages in Vietnam and Cambodia acquired a substitution in E that significantly increased polyclonal neutralization but nonetheless were successful in disseminating and infecting human hosts.This work was supported by the Bill and Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (FIRST Program); the Nicaraguan Pediatric Dengue Cohort Study was supported by the Pediatric Dengue Vaccine Initiative (grant VE-1 to E. H.) and the National Institutes of Health (NIH) R01 AI099631 (to Dr Angel Balmaseda); and L. C. K. was supported by a Gates Cambridge Scholarship and the NIH Oxford-Cambridge Scholars Program

Lovastatin for adult patients with dengue: protocol for a randomised controlled trial.

BACKGROUND: Dengue is the most important vector-borne viral infection of man, with approximately 2 billion people living in areas at risk. Infection results in a range of manifestations from asymptomatic infection through to life-threatening shock and haemorrhage. One of the hallmarks of severe dengue is vascular endothelial disruption. There is currently no specific therapy and clinical management is limited to supportive care. Statins are a class of drug initially developed for lipid lowering. There has been considerable recent interest in their effects beyond lipid lowering. These include anti-inflammatory effects at the endothelium. In addition, it is possible that lovastatin may have an anti-viral effect against dengue. Observational data suggest that the use of statins may improve outcomes for such conditions as sepsis and pneumonia. This paper describes the protocol for a randomised controlled trial investigating a short course of lovastatin therapy in adult patients with dengue. METHODS/DESIGN: A randomised, double-blind, placebo-controlled trial will investigate the effects of lovastatin therapy in the treatment of dengue. The trial will be conducted in two phases with an escalation of dose between phases if an interim safety review is satisfactory. This is an exploratory study focusing on safety and there are no data on which to base a sample size calculation. A target sample size of 300 patients in the second phase, enrolled over two dengue seasons, was chosen based on clinical judgement and feasibility considerations. In a previous randomised trial in dengue, about 10% and 30% of patients experienced at least one serious adverse event or adverse event, respectively. With 300 patients, we will have 80% power to detect an increase of 12% (from 10% to 22%) or 16% (from 30% to 46%) in the frequency of adverse events. Furthermore, this sample size ensures some power to explore the efficacy of statins. DISCUSSION: The development of a dengue therapeutic that can attenuate disease would be an enormous advance in global health. The favourable effects of statins on the endothelium, their good safety profile and their low cost make lovastatin an attractive therapeutic candidate. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN03147572

A linguagem das ciências médicas : traduzir para caracterizar

A Linguagem das Ciências Médicas: traduzir para caracterizar consiste num relatório de estágio realizado durante dois semestres na Onoma – Gabinete de Traduções no âmbito do Mestrado em Tradução da Faculdade de Letras da Universidade de Lisboa. Durante a realização do estágio, foi dada a oportunidade de traduzir textos de variadas áreas de especialidade. Contudo, a grande maioria das traduções realizadas enquadravam-se no domínio das Ciências Médicas e, por esse motivo, o presente relatório incide na sua totalidade em questões de tradução da linguagem de especialidade das Ciências Médicas. O relatório procura caracterizar a linguagem das Ciências Médicas com base nas traduções realizadas durante o estágio. Para tal, o processo de tradução foi caracterizado procurando a identificação de fenómenos linguísticos, o papel da terminologia, a existência de géneros textuais e a comunicação pragmática desta linguagem. Além disso, as considerações tecidas visam a estruturação de uma ferramenta de apoio à abordagem da tradução do discurso das Ciências Médicas, procurando preencher as lacunas sentidas durante a tarefa do tradutor.The Language of Medical Sciences: translate to characterize consists of an Internship Report developed during two semesters at Onoma – Gabinete de Traduções for obtaining the Master Degree in Translation at the Faculty of Letters of the University of Lisbon. During the internship was given the opportunity to translate texts in various areas of expertise. Nevertheless, the majority of the translations assigned to me were from the Medical Sciences domain and, therefore, the following report is totally focused on translation concerns on Medical Sciences specialized language. The report aims to characterize the Medical Sciences language based on the translations done during the internship. Thus, the translation process was characterized with the aim to identify linguistics phenomenon, terminology role, the existence of textual genres and the pragmatic communication of the language in focus. Furthermore, the considerations done intent to structure a supporting tool to approach the translation of Medical Sciences discourse, overcoming difficulties experienced during the translator task

Good Genes and Sexual Selection in Dung Beetles (Onthophagus taurus): Genetic Variance in Egg-to-Adult and Adult Viability

Whether species exhibit significant heritable variation in fitness is central for sexual selection. According to good genes models there must be genetic variation in males leading to variation in offspring fitness if females are to obtain genetic benefits from exercising mate preferences, or by mating multiply. However, sexual selection based on genetic benefits is controversial, and there is limited unambiguous support for the notion that choosy or polyandrous females can increase the chances of producing offspring with high viability. Here we examine the levels of additive genetic variance in two fitness components in the dung beetle Onthophagus taurus. We found significant sire effects on egg-to-adult viability and on son, but not daughter, survival to sexual maturity, as well as moderate coefficients of additive variance in these traits. Moreover, we do not find evidence for sexual antagonism influencing genetic variation for fitness. Our results are consistent with good genes sexual selection, and suggest that both pre- and postcopulatory mate choice, and male competition could provide indirect benefits to females