Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals

Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity

<p>Abstract</p> <p>Background</p> <p>Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination <it>proportional </it>to the population at each point in time.</p> <p>Methods</p> <p>We present a SIR-like model that explicitly takes into account vaccine supply and the <it>number </it>of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the <it>non-proportional </it>model of vaccination and compare it to the proportional scheme typically found in the literature.</p> <p>Results</p> <p>The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity.</p> <p>Conclusions</p> <p>The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing nations with a wide variety of financial and medical resources. Finally, the model can be used by government and medical officials to create customized pandemic preparedness plans based on the supply and administration constraints of specific communities.</p

[Christian pamphlets. Vol. 12]

1 v. ; 24 cm.De scholiis Homericis ad historiam fabularem pertinentibus / Eduardus Schwartz -- Zur Stichometrie / Martin Schanz -- Die Iuli Frontini Strategematon libro qui fertur quarto / Gottholdus Gundermann -- Die Traditionen über die Stiftung der olympischen Spiele / P. Knapp -- Die älteste lateinische Inschrfit / P.K. -- Zu den Biographika des Suidas / Adam Daub -- Beiträge zur Erklärung von Wandbildern / Paul Knapp -- Ueber die Schriften des Cornelius Celsus / M. Schanz -- Zu Theognis / Eduard Hiller -- Index lectionum quae in universitate litter. Friederica Guilelma per sem. hib. 1880/1 habebuntur ; Index scholarum in universitate litter. Vratislaviensi per hiemem anni 1880/1 habendarum / Ludwig Martens -- Friedrich Wieseler, Scenische und kritische Bemerkungen zu Euripides' Kyklops / N. Wecklein.Antonius Jannarakis, Annotationes criticae in Longini qui fertur [peri hypsous] libellum / Ludwig Martens -- De Aristophane Byzantio et Suetonio Tranquillo Eustathi auctoribus / Leopold Cohn // Analecta Aristarchea / Adolfus Schimberg -- De M. Tullii Ciceronis Oratione in toga candida habita / Paulus Koetschau -- De figuris quaestiones criticae Part I. / Iohannes Mueller -- Ausonianarum quaestionum specimen primum / Guilelmus Brandes -- Westfälische Volkslieder in Wort und Weise .. / Reinhold Köhler -- August Reinbrecht, Die Legende von den sieben Schläfern und der anglo-normannische Dichter Chardri / H. Varnhagen -- De tropis et figuris apud Tibullum / Marx Hansen -- Bistânî's Encyclopédie arabe / Fleischer -- Tibetan and English dictionary by H.A. Jäschke / G. Th. Reichelt -- Geschichte des Artachšîr i Pâpakan, aus dem Pehlewi übersetzt ... von T. Nöldeke / Alfred von Gutschmid.Schī-kīng. Das kanonische Liederbuch der Chiesen. Aus dem Chinesischen übersetzt und erklärt von Victor von Strauss / V. von Strauss und Torney -- Bemerkungen zu Tabar's Sasanidengeschichte, übersetzt von Th. Nöldeke / Alfred von Gutschmid -- Fabius Pictor und Livius / Eduard Heydenreich -- De Euripideorum prologorum / Iosephus Klinkenberg -- Über den Codex Laurentianus 53, 35, nebst Nachträgen zu den neuesten Forschungen über Ciceros Briefe / Franz Rühl -- Friedrich Christoph Schlosser / Franz Rühl -- Miscellen -- Kritische Bemerkungen / A. Nauck

Estimates of the reproduction number for seasonal, pandemic, and zoonotic influenza: a systematic review of the literature

International audienceBackground The potential impact of an influenza pandemic can be assessed by calculating a set of transmissibility parameters, the most important being the reproduction number (R), which is defined as the average number of secondary cases generated per typical infectious case. Methods We conducted a systematic review to summarize published estimates of R for pandemic or seasonal influenza and for novel influenza viruses (e.g. H5N1). We retained and summarized papers that estimated R for pandemic or seasonal influenza or for human infections with novel influenza viruses. Results The search yielded 567 papers. Ninety-one papers were retained, and an additional twenty papers were identified from the references of the retained papers. Twenty-four studies reported 51 R values for the 1918 pandemic. The median R value for 1918 was 1.80 (interquartile range [IQR]: 1.47-2.27). Six studies reported seven 1957 pandemic R values. The median R value for 1957 was 1.65 (IQR: 1.53-1.70). Four studies reported seven 1968 pandemic R values. The median R value for 1968 was 1.80 (IQR: 1.56-1.85). Fifty-seven studies reported 78 2009 pandemic R values. The median R value for 2009 was 1.46 (IQR: 1.30-1.70) and was similar across the two waves of illness: 1.46 for the first wave and 1.48 for the second wave. Twenty-four studies reported 47 seasonal epidemic R values. The median R value for seasonal influenza was 1.28 (IQR: 1.19-1.37). Four studies reported six novel influenza R values. Four out of six R values were. Conclusions These R values represent the difference between epidemics that are controllable and cause moderate illness and those causing a significant number of illnesses and requiring intensive mitigation strategies to control. Continued monitoring of R during seasonal and novel influenza outbreaks is needed to document its variation before the next pandemic