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Re-thinking yellow fever vaccines: fighting old foes with new generation vaccines.

Despite the existence of a highly efficient yellow fever vaccine, yellow fever reemergence throughout Africa and the Americas has put 900 million people in 47 countries at risk of contracting the disease. Although the vaccine has been key to controlling yellow fever epidemics, its live-attenuated nature comes with a range of contraindications that prompts advising against its administration to pregnant and lactating women, immunocompromised individuals, and those with hypersensitivity to chicken egg proteins. Additionally, large outbreaks have highlighted problems with insufficient vaccine sup…

Молекулярный механизм защиты от печени при заражении желтой лихорадкой.

Желтая лихорадка (YF) — вирусная геморрагическая лихорадка, которая обычно связана с печенью. В Бразилии недавно произошла самая крупная зарегистрированная вспышка YF, и эта болезнь была смертельной более чем у трети пострадавших лиц, главным образом из-за острой недостаточности печени. Затрагиваемые лица, как правило, лечатся лишь в порядке поддержки, однако во время недавней вспышки заболевания в Бразилии отдельные пациенты получали пересадку печени. Мы воспользовались этим клиническим опытом, чтобы лучше охарактеризовать клинические и патологические особенности побоев печени, вызванных YF,

Совпадение в аннотации оригинала
Yellow fever (YF) is a viral hemorrhagic fever that typically involves the liver. Brazil recently experienced its largest recorded YF outbreak, and the disease was fatal in more than a third of affected individuals, mostly because of acute liver failure. Affected individuals are generally treated only supportively, but during the recent Brazilian outbreak, s…

Eliminating yellow fever epidemics in Africa: Vaccine demand forecast and impact modelling.

BACKGROUND: To counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy. METHODS AND FINDINGS: We developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local …

Phase 1 Trial of a Therapeutic Anti-Yellow Fever Virus Human Antibody.

BACKGROUND: Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America. METHODS: In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety …

Duration of seropositivity following yellow fever vaccination in U.S. military service members.

BACKGROUND: The United States military regularly deploys thousands of service members throughout areas of South America and Africa that are endemic for yellow fever (YF) virus. To determine if booster doses might be needed for service members who are repetitively or continually deployed to YF endemic areas, we evaluated seropositivity among US military personnel receiving a single dose of YF vaccine based on time post-vaccination. METHODS: Serum antibodies were measured using a plaque reduction neutralization test with 50% cutoff in 682 military personnel at 5-39 years post-vaccination. We de…

Preparation and application of yellow fever virus NS1 protein-specific monoclonal antibodies.

Yellow fever is an acute infectious disease that is common in Africa and South America and causes thousands of deaths annually. However, there are very few studies on yellow fever virus (YFV) antigen detection kits. As a detection target, the nonstructural protein 1 (NS1) has been successfully used in the early diagnosis of dengue virus (a member of the Flaviviridae family) infection. In this study, we used monoclonal antibody technology to prepare anti-YFV NS1 monoclonal antibodies (MAbs) and identified their immunological properties. Next, we used two mouse MAbs that can recognize different …

Unilateral acute idiopathic maculopathy secondary to yellow fever disease: a case report.

PURPOSE: To report a case of unilateral acute idiopathic maculopathy (UAIM) associated with yellow fever. OBSERVATIONS: A 59-year-old man presented with acute blurring of his vision 30 days after symptoms of yellow fever virus infection. Findings resembling unilateral acute idiopathic maculopathy of the left eye were noted on ophthalmoscopy, fluorescein angiography and optical coherence tomography. The right eye exam was normal. He was managed conservatively and recovered complete visual function in 8 weeks. CONCLUSIONS: We describe a case of unilateral acute idiopathic maculopathy disease i…

Yellow fever in Brazil threatens successful recovery of endangered golden lion tamarins.

The golden lion tamarin is an endangered primate endemic to Brazil's Atlantic Forest. Centuries of deforestation reduced numbers to a few hundred individuals in isolated forest fragments 80 km from Rio de Janeiro city. Intensive conservation action including reintroduction of zoo-born tamarins into forest fragments 1984-2000, increased numbers to about 3,700 in 2014. Beginning in November 2016, southeastern Brazil experienced the most severe yellow fever epidemic/epizootic in the country in 80 years. In May 2018, we documented the first death of a golden lion tamarin due to yellow fever. We re…

Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report.

BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neut…

Modeling the elevated risk of yellow fever among travelers visiting Brazil, 2018.

BACKGROUND: Unlike the epidemic of yellow fever from 2016 to 17 in Brazil mostly restricted to the States of Minas Gerais and Espirito Santo, the epidemic from 2017 to 18 mainly involved São Paulo and Rio de Janeiro and resulted in multiple international disseminations. To understand mechanisms behind this observation, the present study analyzed the distribution of imported cases from Brazil, 2018. METHODS: A statistical model was employed to capture the risk of importing yellow fever by returning international travelers from Brazil. We estimated the relative risk of importation among travele…

Management and control of yellow fever virus: Brazilian outbreak January-April, 2018.

Yellow fever virus (YFV) has a long history of causing human disease. Today, YFV is persevered in jungle environments with occasional sporadic human outbreaks in South America and periodic intermediate human transmissions with occasional urban outbreaks in sub-Saharan Africa. The ever-present risk of outbreak is primarily controlled for via vaccination coverage to vulnerable human populations. Global vaccine supplies have been strained in the setting of recent outbreaks in Africa and Brazil. The increasingly global community of today has placed an ever-growing tension on the management and con…

Predicting Yellow Fever Through Species Distribution Modeling of Virus, Vector, and Monkeys.

Mapping yellow fever (YF) risk is often based on place of infection of human cases, whereas the circulation between nonhuman primates (NHP) and vectors is neglected. In 2008/2009, YF devastated NHP at the southern limit of the disease in the Americas. In view of the recent expansion of YF in Brazil, we modeled the environmental suitability for YF with data from 2008/2009 epizootic, the distribution of NHP (Alouatta spp.), and the mosquito (Haemagogus leucocelaenus) using the maximum entropy algorithm (Maxent) to define risk areas for YF and their main environmental predictors. We evaluated poi…

T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.

The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the c…

[Severe Yellow fever vaccine-associated disease: a case report and current overview].

History and physical examination A 56-year-old man developed high fever with severe headaches, fatigue, impaired concentration skills, and an exanthema 5 days after a yellow fever (YF) vaccination. Laboratory tests Liver enzymes and YF antibody titers were remarkably elevated. YF vaccine virus was detected in urine by PCR. Diagnosis and therapy Initially, severe YF vaccine-associated visceral disease was suspected and treated symptomatically. Clinical Course His fever ceased after 10 days in total, no organ failure developed. However, postencephalitic symptoms persisted with fatigue and impair…

Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos.

The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution micros…

Human genetic variation and yellow fever mortality during 19th century U.S. epidemics.

UNLABELLED: We calculated the incidence, mortality, and case fatality rates for Caucasians and non-Caucasians during 19th century yellow fever (YF) epidemics in the United States and determined statistical significance for differences in the rates in different populations. We evaluated nongenetic host factors, including socioeconomic, environmental, cultural, demographic, and acquired immunity status that could have influenced these differences. While differences in incidence rates were not significant between Caucasians and non-Caucasians, differences in mortality and case fatality rates were…

Biological and phylogenetic characteristics of yellow fever virus lineages from West Africa.

The yellow fever virus (YFV), the first proven human-pathogenic virus, although isolated in 1927, is still a major public health problem, especially in West Africa where it causes outbreaks every year. Nevertheless, little is known about its genetic diversity and evolutionary dynamics, mainly due to a limited number of genomic sequences from wild virus isolates. In this study, we analyzed the phylogenetic relationships of 24 full-length genomes from YFV strains isolated between 1973 and 2005 in a sylvatic context of West Africa, including 14 isolates that had previously not been sequenced. By …

The small nuclear ribonucleoprotein U1A interacts with NS5 from yellow fever virus.

The flavivirus NS5 protein is one of the most important proteins of the replication complex, and cellular proteins can interact with it. This study shows for the first time that the yellow fever virus (YFV) NS5 protein is able to interact with U1A, a protein involved in splicing and polyadenylation. We confirmed this interaction by GST-pulldown assay and by co-immunoprecipitation in YFV-infected cells. A region between amino acids 368 and 448 was identified as the site of interaction of the NS5 protein with U1A. This region was conserved among some flaviviruses of medical importance. The impli…

Household-based sero-epidemiologic survey after a yellow fever epidemic, Sudan, 2005.

From September through early December 2005, an outbreak of yellow fever (YF) occurred in South Kordofan, Sudan, resulting in a mass YF vaccination campaign. In late December 2005, we conducted a serosurvey to assess YF vaccine coverage and to better define the epidemiology of the outbreak in an index village. Of 552 persons enrolled, 95% reported recent YF vaccination, and 25% reported febrile illness during the outbreak period: 13% reported YF-like illness, 4% reported severe YF-like illness, and 12% reported chikungunya-like illness. Of 87 persons who provided blood samples, all had positive…