679 research outputs found

    The Breadth of Viruses in Human Semen.

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    Zika virus RNA is frequently detected in the semen of men after Zika virus infection. To learn more about persistence of viruses in genital fluids, we searched PubMed for relevant articles. We found evidence that 27 viruses, across a broad range of virus families, can be found in human semen

    A boarding school outbreak of pertussis in adolescents : value of laboratory diagnostic methods

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    Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P&lt;0&middot;001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.<br /

    Fuzzy support vector machines for pattern classification

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    In response to the Ebola virus disease (EVD) outbreak in West Africa, the World Health Organization has advised all nations to prepare for the detection, investigation and management of confirmed and suspected EVD cases in order to prevent further spread through international travel. To gain insights into the state of preparedness of European hospitals, an electronic survey was circulated in August–September 2014 to 984 medical professionals representing 736 hospitals in 40 countries. The survey addressed the willingness and capacity to admit patients with suspected EVD as well as specific preparedness activities in response to the current Ebola crisis. Evaluable responses were received from representatives of 254 (32%) hospitals in 38 countries, mostly tertiary care centres, of which 46% indicated that they would admit patients with suspected EVD. Patient transfer agreements were in place for the majority of hospitals that would not admit patients. Compared with non-admitting hospitals, admitting hospitals were more frequently engaged in various preparedness activities and more often contained basic infrastructural characteristics such as admission rooms and laboratories considered important for infection control, but some gaps and concerns were also identified. The results of this survey help to provide direction towards further preparedness activities and prioritisation thereof

    Pharmacokinetics of TKM-130803 in Sierra Leonean patients with Ebola virus disease: plasma concentrations exceed target levels, with drug accumulation in the most severe patients

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    Background: TKM-130803 is a specific anti-EBOV therapeutic comprised of two small interfering RNAs (siRNA) siLpol-2 and siVP35-2. The pharmacokinetics (PK) of these siRNAs was defined in Ebola virus disease (EVD) patients, with reference to efficacy (ET) and toxicology thresholds (TT). The relationship between PK and patient survival was explored. Methods: Pharmacokinetic (PK) and pharmacodynamic (PD) data were available for seven participants with EVD in Sierra Leone who received 0·3 mg/kg of TKM-130803 by intravenous infusion over 2 h daily for up to 7 days. Plasma concentration of siRNA was compared to survival at 14 days. PK data were fitted to two-compartment models then Monte Carlo simulated PK profiles were compared to ET (Cmax 0·04–0·57 ng/mL and mean concentration 1·43 ng/mL), and TT (3000 ng/mL). Findings: Viral loads (VL) were not significantly different at treatment onset or during treatment (p = 0·1) in subjects who survived or died. siRNA was in quantitative excess of virus genomes throughout treatment, but the 95% percentile exceeded TT. The maximum AUC for which the 95% percentile remained under TT was a continuous infusion of 0·15 mg/kg/day. Plasma concentration of both siRNAs were higher in subjects who died compared to subjects who survived (p&lt;0·025 both siRNAs). Interpretation: TKM-130803 was circulating in molar excess of circulating virus; a level considered needed for efficacy. Given extremely high viral loads it seems likely that the patients died because they were physiologically beyond the point of no return. Subjects who died exhibited some indication of impaired drug clearance, justifying caution in dosing strategies for such patients. This analysis has given a useful insight into the pharmacokinetics of the siRNA in the disease state and illustrates the value of designing PKPD studies into future clinical trials in epidemic situations. Funding: This work was supported by the Wellcome Trust of Great Britain (grant number 106491/Z/14/Z and 097997/Z/11/A) and by the EU FP7 project PREPARE (602525). The PHE laboratory was funded by the UK Department for International Development. The funders had no role in trial design, data collection or analysis. The views expressed are those of the authors and not necessarily those of Public Health England, the Department of Health, or the EU. Trial registration: Pan African Clinical Trials Registry PACTR201501000997429

    Potential health and economic impacts of dexamethasone treatment for patients with COVID-19

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    Dexamethasone can reduce mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively. Here, we estimate the potential number of lives saved and life years gained if this treatment were to be rolled out in the UK and globally, as well as the cost-effectiveness of implementing this intervention. Assuming SARS-CoV-2 exposure levels of 5% to 15%, we estimate that, for the UK, approximately 12,000 (4,250 - 27,000) lives could be saved between July and December 2020. Assuming that dexamethasone has a similar effect size in settings where access to oxygen therapies is limited, this would translate into approximately 650,000 (240,000 - 1,400,000) lives saved globally over the same time period. If dexamethasone acts differently in these settings, the impact could be less than half of this value. To estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to perform clinical research in settings with limited access to oxygen and/or ventilators, for example in low- and middle-income countries

    Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies

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    Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed

    Интеллектуальная радиосеть с нечеткой конфигурацией

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    В статье обсуждаются возможности применения одноранговой радиосети стандарта IEEE 802.15.4 (ZigBee) диапазона 2,4 ГГц для работы системы, состоящей из группы малогабаритных мобильных роботов и одного командного пункта. Основная задача группы роботов – проведение разведки во время спасательных операций после техногенных и природных катастроф и аварий. Для сохранения управляемости отдельными роботами и системой в целом предлагается повысить «интеллект» системы связи за счет гибкой маршрутизации каналов между командным пунктом и конкретным мобильным роботом с тем, чтобы иметь систему с автоматическим, интеллектуальным восстановлением канала обмена данных.У статті обговорюються можливості застосування однорангової радіомережі стандарту ІЕЕ 802.15.4 (ZigBee) діапазону 2,4 Ггу для роботи системи, що складається з групи малогабаритних мобільних роботів та одного командного пункту. Основна задача групи роботів – проведення розвідки під час рятувальних операцій після техногенних та природних катастроф і аварій. Для збереження керованості окремими ротами та системою в цілому пропонується підвищити інтелект системи зв’язку за рахунок гнучкої маршрутитизації каналів між командним пунктом та конкретним мобільним роботом з тим, щоб мати систему з автоматичним, інтелектуальним відновлюванням каналу обміну даних.In the article the possibilities of application peer-to-peer radio networks of standard IEEE 802.15.4 (ZigBee) a range of 2,4 GHz for work of the system consisting of small-sized mobile robots group and one command point are discussed. The primary goal of group of robots – is carrying out of investigation during rescue operations after technogenic and natural accidents and failures. For controllability preservation by separate robots and system as a whole, it is offered to raise “intelligence” of a communication system at the expense of flexible routeing of channels between command point and the concrete mobile robot to have system with automatic, intellectual restoration of the channel of data exchange
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