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Spatial epidemiology of yellow fever: Identification of determinants of the 2016-2018 epidemics and at-risk areas in Brazil.

Optimise control strategies of infectious diseases, identify factors that favour the circulation of pathogens, and propose risk maps are crucial challenges for global health. Ecological niche modelling, once relying on an adequate framework and environmental descriptors can be a helpful tool for such purposes. Despite the existence of a vaccine, yellow fever (YF) is still a public health issue. Brazil faced massive sylvatic YF outbreaks from the end of 2016 up to mid-2018, but cases in human and non-human primates have been recorded until the beginning of 2020. Here we used both human and monk…

Double Lock of a Human Neutralizing and Protective Monoclonal Antibody Targeting the Yellow Fever Virus Envelope.

Yellow fever virus (YFV), a deadly human pathogen, is the prototype of the genus Flavivirus. Recently, YFV re-emerged in Africa and Brazil, leading to hundreds of deaths, with some cases imported to China. Prophylactic or therapeutic countermeasures are urgently needed. Previously, several human monoclonal antibodies against YFV were screened out by phage display. Here, we find that one of them, 5A, exhibits high neutralizing potency and good protection. Crystallographic analysis of the YFV envelope (E) protein in its pre- and post-fusion states shows conformations similar to those observed in…

Antibody responses to yellow fever vaccine in 9 to 11-month-old Malian and Ghanaian children.

Background: The World Health Organization recommends use of a single yellow fever (YF) vaccine dose for life and fractional doses in outbreaks when there are limited vaccine stocks. In endemic regions, this vaccine is given as part of routine infant immunization programs around 9 months of age. There is a need to better understand immune responses when vaccinating infants particularly in contexts where the child may be malnourished. Methods: Data from 393 Malian and Ghanaian infants who concomitantly received measles and YF vaccines at 9 to 11 months of age were retrospectively analyzed. Respo…

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate.

The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF). Screening of excipients was performed in …

Efficacy of sofosbuvir as treatment for yellow fever: protocol for a randomised controlled trial in Brazil (SOFFA study).

INTRODUCTION: An ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YF. This is a multicentre open-label randomised controlled trial wi…

Yellow fever cases in French Guiana, evidence of an active circulation in the Guiana Shield, 2017 and 2018.

French Guiana (FG) is a French overseas region bordering Brazil and Suriname that is considered endemic for yellow fever (YF); vaccination is compulsory for residents and travellers. In August 2017 and 2018, two sporadic YF cases were notified 1 year apart, confirming that sylvatic YF virus circulation is active in the region. YF vaccination coverage should be closely monitored and improved in FG and neighbouring territories and clinicians should be aware of the risk.

Торговля, конфликты и загрязнение: желтая лихорадка в ранней независимости Веракрус в США воображаемый, 1821 - 1848 годы.

В то время как торговые связи между Мексикой и Соединенными Штатами через портовый город Веракрус принесли значительные экономические и социальные преимущества в начале XIX века, проблемы общественного здравоохранения в связи с желтой лихорадкой вызывали восхищение и страх среди американской аудитории (на юге и востоке портовых городов) с момента установления мира до вторжения США в Мексику и оккупации ею Мексики (1846-1848 годы). В этой статье рассматриваются сложные связи между торговлей, конфликтами и загрязнением в связи с портовым городом Веракрус и Соединенными Штатами в первые десятилет

Совпадение в аннотации оригинала
While commercial links between Mexico and the United States through the port city of Veracruz brought significant economic and social advantages in the early nineteenth century, public health concerns around yellow fever produced fascination and fear among US audiences (in southern and eastern port cities) from times of peace until the US invasion and occupa…

Identification of Dengue and Chikungunya Cases Among Suspected Cases of Yellow Fever in the Democratic Republic of the Congo.

For more than 95% of acute febrile jaundice cases identified through surveillance for yellow fever, a reemerging arthropod-borne viral disease, no etiological exploration is ever done. The aim of this study was to test for other arthropod-borne viruses that can induce the same symptoms in patients enrolled in the yellow fever surveillance in the Democratic Republic of the Congo (DRC). Of 652 patients included in the surveillance of yellow fever in DRC from January 2003 to January 2012, 453 patients that tested negative for yellow fever virus (YFV) immunoglobulin M (IgM) antibodies were selecte…

Access to yellow fever travel vaccination centres in England, Wales, and Northern Ireland: A geographical study.

BACKGROUND: More than 700,000 trips were made by residents in England, Wales, and Northern Ireland (EWNI) in 2015 to tropical countries endemic for yellow fever, a potentially deadly, yet vaccine-preventable disease transmitted by mosquitoes. The aim of this study was to map the geographical accessibility of yellow fever vaccination centres (YFVC) in EWNI. METHODS: The location of 3208 YFVC were geocoded and the average geodetic distance to nearest YFVC was calculated for each population unit. Data on trips abroad and centres were obtained regionally for EWNI and nationally for the World Top2…

Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

AIMS: To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. METHODS AND RESULTS: Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation …

Development and validation of an ELISA kit (YF MAC-HD) to detect IgM to yellow fever virus.

Yellow fever virus (YFV) is endemic in tropical and sub-tropical regions of the world, with around 180,000 human infections a year occurring in Africa. Serologic testing is the chief laboratory diagnostic means of identifying an outbreak and to inform the decision to commence a vaccination campaign. The World Health Organization disseminates the reagents for YFV testing to African reference laboratories, and the US Centers for Disease Control and Prevention (CDC) is charged with producing and providing these reagents. The CDC M-antibody capture ELISA is a 2-day test, requiring titration of rea…

Survival and swimming behavior of insecticide-exposed larvae and pupae of the yellow fever mosquito Aedes aegypti.

BACKGROUND: The yellow fever mosquito Aedes aegypti is essentially a container-inhabiting species that is closely associated with urban areas. This species is a vector of human pathogens, including dengue and yellow fever viruses, and its control is of paramount importance for disease prevention. Insecticide use against mosquito juvenile stages (i.e. larvae and pupae) is growing in importance, particularly due to the ever-growing problems of resistance to adult-targeted insecticides and human safety concerns regarding such use in human dwellings. However, insecticide effects on insects in gene…

The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases.

BACKGROUND: Like many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission. METHODS: We compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011. We used a Bayesian model to estimate the probability of each infection outcome. RESULTS: For YF virus infecti…

Synthesis and evaluation of imidazole-4,5- and pyrazine-2,3-dicarboxamides targeting dengue and yellow fever virus.

The results of a high-throughput screening assay using the dengue virus-2 replicon showed that the imidazole 4,5-dicarboxamide (I45DC) derivative (15a) has a high dengue virus inhibitory activity. Based on 15a as a lead compound, a novel class of both disubstituted I45DCs and the resembling pyrazine 2,3-dicarboxamides (P23DCs) were synthesized. Here, we report on their in vitro inhibitory activity against dengue virus (DENV) and yellow fever virus (YFV). Some of these first generation compounds have shown activity against both viruses in the micromolar range. Within this series, compound 15b w…

Swarming mechanisms in the yellow fever mosquito: aggregation pheromones are involved in the mating behavior of Aedes aegypti.

Mosquitoes of various species mate in swarms comprised of tens of thousands of flying males. In this study, we examined Aedes aegypti swarming behavior and identified associated chemical cues. Novel evidence is provided that Ae. aegypti females aggregate by means of olfactory cues, such as aggregation pheromones. Isolation of Ae. aegypti aggregation pheromones was achieved by aeration of confined mosquitoes and collection of associated volatiles by glass filters. The collected volatiles were identified through gas chromatography mass spectrometry (GCMS). Three aggregation pheromones were colle

Binding of a fluorescence reporter and a ligand to an odorant-binding protein of the yellow fever mosquito, Aedes aegypti.

Odorant-binding proteins (OBPs), also named pheromone-binding proteins when the odorant is a pheromone, are essential for insect olfaction. … ocket. A high school research project was aimed at testing whether the orthologous protein from the yellow fever mosquito, AaegOBP1, binds DEET and other insect repellents, and MOP was used as a positive control. Binding assays using the fluorescence reporter N-phenyl-1-naphtylamine (NPN) were inconclusive. However, titration of NPN fluorescence emission in Aa …

Historical analysis of the records of sylvan yellow fever in the State of Amazonas, Brazil, from 1996 to 2009.

INTRODUCTION: Yellow fever is a non-contagious infectious disease, highly lethal, transmitted by the Aedes, Haemagogus and Sabethes. METHODS: Descriptive retrospective study of the yellow fever cases in Amazonas, between 1996 and 2009. RESULTS: Forty two cases of yellow fever were confirmed, with 30 deaths, 10% of which were foreigners. CONCLUSIONS: The presence of Aedes aegypti and Aedes albopictus in both rural Amazonas and its capital demonstrates the dispersion of these vectors and underscores the need for better and continuous epidemiological and entomological control.

Roles of PKC and phospho-adducin in transepithelial fluid secretion by Malpighian tubules of the yellow fever mosquito.

The diuretic hormone aedeskinin-III is known to increase the paracellular Cl- conductance in Malpighian (renal) tubules of the mosquito Aedes aegypti via a G protein-coupled receptor. The increase serves the blood-meal-initiated diuresis and is associated with elevated levels of Ca2+ and phosphorylated adducin in the cytosol of tubule. In the present study we have cloned adducin in Aedes Malpighian tubules and investigated its physiological roles. Immunolabeling experiments are consistent with the association of adducin with the cortical cytoskeleton, especially near the apical brush border of

Ovary ecdysteroidogenic hormone functions independently of the insulin receptor in the yellow fever mosquito, Aedes aegypti.

Most mosquito species must feed on the blood of a vertebrate host to produce eggs. In the yellow fever mosquito, Aedes aegypti, blood feeding triggers medial neurosecretory cells in the brain to release insulin-like peptides (ILPs) and ovary ecdysteroidogenic hormone (OEH). Theses hormones thereafter directly induce the ovaries to produce ecdysteroid hormone (ECD), which activates the synthesis of yolk proteins in the fat body for uptake by oocytes. ILP3 stimulates ECD production by binding to the mosquito insulin receptor (MIR). In contrast, little is known about the mode of action of OEH, wh…