Explore the vast range of titles available.

Recent outbreaks between 2015–17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants. In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18–60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1:1:1:1) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination. All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12–36] vs 28% [five of 18 participants, 10–54]), and erythema (13% [seven of 54 participants, 5–25] vs 39% [seven of 18 participants, 17–64]), with headache (32% [17 of 54 participants, 20–46] vs 44% [eight of 18 participants, 22–69]) and malaise (26% [14 of 54 participants, 15–40] vs 33% [six of 18 participants, 13–59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82–100), 89% (16 participants, 65–99), 100% (18 participants, 82–100), and 94% (17 participants, 73–100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID50 groups, and YF-VAX group, respectively, remained seroprotected through D180. vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development. Sanofi.

\" It is no exaggeration to say that the Hankey, a small British ship that circled the Atlantic in 1792 and 1793, transformed the history of the Atlantic world. This extraordinary book uncovers the long-forgotten story of the Hankey, from its altruistic beginnings to its disastrous end, and describes the ship's fateful impact upon people from West Africa to Philadelphia, Haiti to London. Billy G. Smith chased the story of the Hankey from archive to archive across several continents, and he now brings back to light a saga that continues to haunt the modern world. It began with a group of high-minded British colonists who planned to establish a colony free of slavery in West Africa. With the colony failing, the ship set sail for the Caribbean and then North America, carrying, as it turned out, mosquitoes infected with yellow fever. The resulting pandemic as the Hankey traveled from one port to the next was catastrophic. In the United States, tens of thousands died in Philadelphia, New York, Boston, and Charleston. The few survivors on the Hankey eventually limped back to London, hopes dashed and numbers decimated. Smith links the voyage and its deadly cargo to some of the most significant events of the era-the success of the Haitian slave revolution, Napoleon's decision to sell the Louisiana Territory, a change in the geopolitical situation of the new United States-and spins a riveting tale of unintended consequences and the legacy of slavery that will not die\"-- Provided by publisher.

Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown. In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than -10 percentage points. A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, -5.0 to 5.1) in the intention-to-treat population and -1.9 percentage points (95% CI, -7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, -5.0 to 5.1) and -1.8 percentage points (95% CI, -6.7 to 3.2), and those between the 250-IU dose and the standard dose were -4.4 percentage points (95% CI, -9.4 to 0.7) and -6.7 percentage points (95% CI, -11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups. A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; NIFTY ClinicalTrials.gov number, NCT04059471.).

Tells the tale of five of history's most critical contagions and the havoc these diseases wreaked across the globe, including the bubonic plague, yellow fever, smallpox, Spanish influenza, and AIDS.

•A 2009 Bio-Manguinhos/Fiocruz YF vaccine dose–response study supported WHO's position for fractional dose for outbreaks.•Part of the original cohort was reassessed for immunity duration and seroconversion.•Seroconversion lasted 10 years.•Reduced doses have shown effective seroconversion (>80 %).•Antibody titers in reduced-dose versus full-dose groups remain equivalent. A single dose of standard yellow fever (YF) vaccine is considered to provide life-long protection. In this study, we evaluate the seropositivity conferred by lower doses 10 years post-vaccination. In 2009, Bio-Manguinhos/Fiocruz performed a dose–response study with the 17DD yellow fever vaccine, administering the vaccine in the usual mean dose of 27.476 IU and in decreasing doses (10.447 IU, 3.013 IU, 587 IU, 158 IU and 31 IU), with the usual volume and route (0,5 ml subcutaneous). The decreasing doses were obtained by dilution in the laboratory of the manufacturer and the lots in test had standard quality control and were produced by good manufacturing practices (GMP). Around 30 days after the vaccination, doses down to 587 IU had similar immunogenicity and the 158 IU and 31 IU were inferior to the full dose. The seropositivity was maintained for 10 months, except on the 31 IU group. Eight years after, 85 % of 318 participants evaluated in a follow-up, maintained seropositivity that was similar across groups. Consistently, antibody titers in the reduced-dose groups were also comparable to those of the full-dose group. The current study, 10 years later, showed similarity between the vaccine groups (six arms who received the YF vaccine in decreasing doses: 27.476 IU, 10.447 IU, 3.013 IU, 587 IU, 158 IU, 31 IU) both in relation of seropositivity and in the evaluation of the geometric mean titers. The seropositivity rates across subgroups were 83,1%, 90 %, 87 %, 93 %, 83,8% and 85 %, correspondingly. These findings provides further support to the long-term immunogenicity of lower doses. Clinical trial registry: NCT04416477.

The writings of Hearn's American years reveal an omnivorous curiosity and an always eclectic sensibility. Some Chinese Ghosts (1887) is a stylized retelling of ancient legends, foreshadowing Hearn's later fascination with Asian themes. The exquisitely crafted novels Chita (1889), about the devastation wrought by a Louisiana hurricane, and Youma (1890) about a slave rebellion in Martinique, epitomize his writing at its most luxuriantly romantic. His extraordinary travel book Two Years in the French West Indies (1890) provides a richly impressionistic account of his long stay on Martinique and other Caribbean islands.

Stocks of yellow fever vaccine are insufficient to cover exceptional demands for outbreak response. Fractional dosing has shown efficacy, but evidence is limited to the 17DD substrain vaccine. We assessed the immunogenicity and safety of one-fifth fractional dose compared with standard dose of four WHO-prequalified yellow fever vaccines produced from three substrains. We did this randomised, double-blind, non-inferiority trial at research centres in Mbarara, Uganda, and Kilifi, Kenya. Eligible participants were aged 18–59 years, had no contraindications for vaccination, were not pregnant or lactating, had no history of yellow fever vaccination or infection, and did not require yellow fever vaccination for travel. Eligible participants were recruited from communities and randomly assigned to one of eight groups, corresponding to the four vaccines at standard or fractional dose. The vaccine was administered subcutaneously by nurses who were not masked to treatment, but participants and other study personnel were masked to vaccine allocation. The primary outcome was proportion of participants with seroconversion 28 days after vaccination. Seroconversion was defined as post-vaccination neutralising antibody titres at least 4 times pre-vaccination measurement measured by 50% plaque reduction neutralisation test (PRNT50). We defined non-inferiority as less than 10% decrease in seroconversion in fractional compared with standard dose groups 28 days after vaccination. The primary outcome was measured in the per-protocol population, and safety analyses included all vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT02991495. Between Nov 6, 2017, and Feb 21, 2018, 1029 participants were assessed for inclusion. 69 people were ineligible, and 960 participants were enrolled and randomly assigned to vaccine manufacturer and dose (120 to Bio-Manguinhos-Fiocruz standard dose, 120 to Bio-Manguinhos-Fiocruz fractional dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides standard dose, 120 to Chumakov Institute of Poliomyelitis and Viral Encephalitides fractional dose, 120 to Institut Pasteur Dakar standard dose, 120 to Institut Pasteur Dakar fractional dose, 120 to Sanofi Pasteur standard dose, and 120 to Sanofi Pasteur fractional dose). 49 participants had detectable PRNT50 at baseline and 11 had missing PRNT50 results at baseline or 28 days. 900 were included in the per-protocol analysis. 959 participants were included in the safety analysis. The absolute difference in seroconversion between fractional and standard doses by vaccine was 1·71% (95% CI −2·60 to 5·28) for Bio-Manguinhos-Fiocruz, −0·90% (–4·24 to 3·13) for Chumakov Institute of Poliomyelitis and Viral Encephalitides, 1·82% (–2·75 to 5·39) for Institut Pasteur Dakar, and 0·0% (–3·32 to 3·29) for Sanofi Pasteur. Fractional doses from all four vaccines met the non-inferiority criterion. The most common treatment-related adverse events were headache (22·2%), fatigue (13·7%), myalgia (13·3%) and self-reported fever (9·0%). There were no study-vaccine related serious adverse events. Fractional doses of all WHO-prequalified yellow fever vaccines were non-inferior to the standard dose in inducing seroconversion 28 days after vaccination, with no major safety concerns. These results support the use of fractional dosage in the general adult population for outbreak response in situations of vaccine shortage. The study was funded by Médecins Sans Frontières Foundation, Wellcome Trust (grant no. 092654), and the UK Department for International Development. Vaccines were donated in kind.

\"This book explores the links among ecology, disease, and international politics in the context of the Greater Caribbean - the landscapes lying between Surinam and the Chesapeake - in the seventeenth through early twentieth centuries. Ecological changes made these landscapes especially suitable for the vector mosquitoes of yellow fever and malaria, and these diseases wrought systematic havoc among armies and would-be settlers. Because yellow fever confers immunity on survivors of the disease, and because malaria confers resistance, these diseases played partisan roles in the struggles for empire and revolution, attacking some populations more severely than others. In particular, yellow fever and malaria attacked newcomers to the region, which helped keep the Spanish Empire Spanish in the face of predatory rivals in the seventeenth and early eighteenth centuries. In the late eighteenth and through the nineteenth century, these diseases helped revolutions to succeed by decimating forces sent out from Europe to prevent them\"--Provided by publisher.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.