#Nucleoside Analogs with #Antiviral Activity Against #YellowFever Virus (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents ahd Chemotherapy, full page: (LINK). Abstract, edited.]

Nucleoside Analogs with Antiviral Activity Against Yellow Fever Virus

Keivan Zandi, Franck Amblard, Sarah Amichai, Leda Bassit, Sijia Tao, Yong Jiang, Longhu Zhou, Olivia Ollinger Russell, Seema Mengshetti, Raymond F. Schinazi

DOI: 10.1128/AAC.00889-19

 

ABSTRACT

Yellow fever virus (YFV) is a human flavivirus re-emerging in parts of the world. While a vaccine is available, large outbreaks have recently occurred in Brazil and certain African countries. Development of effective antiviral against YFV is crucial as there is no available effective drug against YFV. We have identified several novel nucleoside analogs with potent antiviral activity against YFV with EC50 values between 0.25 to 1 μM with selectivity indices over 100 in culture.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Yellow fever.

——

Advertisements

Boosting #Global #YellowFever #Vaccine #Supply for #Epidemic #Preparedness: 3 Actions for #China and the #USA (Virol Sin., abstract)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Boosting Global Yellow Fever Vaccine Supply for Epidemic Preparedness: 3 Actions for China and the USA

Authors: Daniel R. Lucey, Kristen R. Kent

Perspective / First Online: 24 May 2019

___

Yellow fever (YF) is an acute disease caused by a flavivirus that infects the liver. It can cause jaundice, bleeding, kidney damage, and death. No antiviral therapy exists. A vaccine does exist, however, and fortunately confers life-long immunity after a single dose (Monath et al.2016; WHO 2017a, b).

(…)

___

Notes

Compliance with Ethical Standards

Conflict of interest: The authors declare that they have no conflict of interest.

Animal and Human Rights Statement: This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Yellow Fever; Vaccines; USA; China.

——

#Serological #evidence of #Flavivirus #circulation in #human populations in Northern #Kenya: an assessment of disease risk 2016-2017 (Virol J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virol J. 2019 May 17;16(1):65. doi: 10.1186/s12985-019-1176-y.

Serological evidence of Flavivirus circulation in human populations in Northern Kenya: an assessment of disease risk 2016-2017.

Chepkorir E1,2, Tchouassi DP3, Konongoi SL4, Lutomiah J4, Tigoi C3, Irura Z5, Eyase F6, Venter M7, Sang R3.

Author information: 1 International Centre of Insect Physiology and Ecology, P. O. Box 30772-00100, Nairobi, Kenya. echepkorir@icipe.org. 2 Center for Viral Zoonoses, Department of Medical Virology, University of Pretoria, P. O. Box 323, Arcadia, 0007, South Africa. echepkorir@icipe.org. 3 International Centre of Insect Physiology and Ecology, P. O. Box 30772-00100, Nairobi, Kenya. 4 Center for Virus Research, Kenya Medical Research Institute, P. O. Box 54628-00200, Nairobi, Kenya. 5 Division of Disease Surveillance and Response, Ministry of Health, P. O. Box 20781-00202, Nairobi, Kenya. 6 Jomo Kenyatta University of Agriculture and Technology, P.O. Box 606, Village Market, Nairobi, Kenya. 7 Center for Viral Zoonoses, Department of Medical Virology, University of Pretoria, P. O. Box 323, Arcadia, 0007, South Africa.

 

Abstract

BACKGROUND:

Yellow fever, Dengue, West Nile and Zika viruses are re-emerging mosquito-borne Flaviviruses of public health concern. However, the extent of human exposure to these viruses and associated disease burden in Kenya and Africa at large remains unknown. We assessed the seroprevalence of Yellow fever and other Flaviviruses in human populations in West Pokot and Turkana Counties of Kenya. These areas border Uganda, South Sudan and Ethiopia where recent outbreaks of Yellow fever and Dengue have been reported, with possibility of spillover to Kenya.

METHODOLOGY:

Human serum samples collected through a cross-sectional survey in West Pokot and Turkana Counties were screened for neutralizing antibodies to Yellow fever, Dengue-2, West Nile and Zika virus using the Plaque Reduction Neutralization Test (PRNT). Seroprevalence was compared by county, site and important human demographic characteristics. Adjusted odds ratios (aOR) were estimated using Firth logistic regression model.

RESULTS:

Of 877 samples tested, 127 neutralized with at least one of the four flaviviruses (14.5, 95% CI 12.3-17.0%), with a higher proportion in Turkana (21.1%, n = 87/413) than in West Pokot (8.6%, n = 40/464). Zika virus seroprevalence was significantly higher in West Pokot (7.11%) than in Turkana County (0.24%; χ2 P < 0.0001). A significantly higher Yellow fever virus seroprevalence was also observed in Turkana (10.7%) compared to West Pokot (1.29%; χ2 P < 0.0001). A high prevalence of West Nile virus was detected in Turkana County only (10.2%) while Dengue was only detected in one sample, from West Pokot. The odds of infection with West Nile virus was significantly higher in males than in females (aOR = 2.55, 95% CI 1.22-5.34). Similarly, the risk of Zika virus infection in West Pokot was twice higher in males than females (aOR = 2.01, 95% CI 0.91-4.41).

CONCLUSION:

Evidence of neutralizing antibodies to West Nile and Zika viruses indicates that they have been circulating undetected in human populations in these areas. While the observed Yellow Fever prevalence in Turkana and West Pokot Counties may imply virus activity, we speculate that this could also be as a result of vaccination following the Yellow Fever outbreak in the Omo river valley, South Sudan and Uganda across the border.

KEYWORDS: Dengue virus; Flaviviruses risk assessment; Northern Kenya; Plaque reduction neutralization test; Seroprevalence; West Nile virus; Yellow fever virus; Zika virus

PMID: 31101058 DOI: 10.1186/s12985-019-1176-y

Keywords: Flavivirus; WNV; Zika Virus; Dengue Fever; Yellow Fever; Serology; Seroprevalence; Kenya.

——

#Predictors of #mortality in patients with #yellowfever: an observational cohort study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Predictors of mortality in patients with yellow fever: an observational cohort study

Prof Esper G Kallas, PhD, Luiz Gonzaga F A B D’Elia Zanella, MD, Carlos Henrique V Moreira, MD, Renata Buccheri, MD, Gabriela B F Diniz, MD, Anna Carla P Castiñeiras, MD, Priscilla R Costa, PhD, Juliana Z C Dias, PhD, Mariana P Marmorato, BSc, Alice T W Song, PhD, Alvino Maestri, PhD, Igor C Borges, PhD, Daniel Joelsons, MD, Natalia B Cerqueira, BSc, Nathália C Santiago e Souza, BSc, Ingra Morales Claro, BSc, Ester C Sabino, PhD, José Eduardo Levi, PhD, Vivian I Avelino-Silva, PhD, Yeh-Li Ho, PhD

Published: May 16, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30125-2

 

Summary

Background

Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of São Paulo city, Brazil.

Methods

In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in São Paolo—the Hospital das Clínicas, University of São Paulo and the Infectious Diseases Institute “Emilio Ribas”. Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death).

Findings

Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clínicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute “Emilio Ribas”. 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5·1 log 10 copies/mL or greater died (95% CI 72–100), compared with only three (11%) of 27 (95% CI 2–29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5·1 log 10 copies/mL.

Interpretation

We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever.

Funding

São Paulo Research Foundation (FAPESP).

Keywords: Yellow Fever; Brazil.

——

Detection of #YellowFever Virus in #Sylvatic #Mosquitoes during Disease #Outbreaks of 2017⁻2018 in Minas Gerais State, #Brazil (Insects, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Insects. 2019 May 10;10(5). pii: E136. doi: 10.3390/insects10050136.

Detection of Yellow Fever Virus in Sylvatic Mosquitoes during Disease Outbreaks of 2017⁻2018 in Minas Gerais State, Brazil.

Pinheiro GG1,2, Rocha MN3, de Oliveira MA4, Moreira LA5, Andrade Filho JD6.

Author information: 1 Coleção de Mosquitos Neotropicais, Instituto René Rachou, Avenida Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil. ggarciapinheiro@gmail.com. 2 Grupo de Estudos em Leishmanioses, Instituto René Rachou, Avenida Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil. ggarciapinheiro@gmail.com. 3 Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Instituto René Rachou, Avenida Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil. marcele.rocha@fiocruz.br. 4 Coleção de Mosquitos Neotropicais, Instituto René Rachou, Avenida Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil. angelica.oliveira@fiocruz.br. 5 Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Instituto René Rachou, Avenida Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil. luciano.andrade@fiocruz.br. 6 Grupo de Estudos em Leishmanioses, Instituto René Rachou, Avenida Augusto de Lima, 1715, Belo Horizonte 30190-002, Brazil. jose.andrade@fiocruz.br.

 

Abstract

Brazil has experienced several arbovirus outbreaks in recent years, among which yellow fever stands out. The state of Minas Gerais faced outbreaks of sylvatic yellow fever in 2017 and 2018, with 1002 confirmed cases and 340 deaths. This work presents the results of survey efforts to detect the yellow fever virus in mosquitoes from two conservation areas in the metropolitan region of Belo Horizonte, Brazil. A total of 867 mosquitoes of 20 species were collected between September 2017 and May 2018, the most abundant being Psorophora(Janthinosoma) ferox (von Humboldt, 1819) (31.3%), Limatus durhamii Theobald, 1901 (19.1%) and Haemagogus (Haemagogus) janthinomys Dyar, 1921 (18.2%). Total RNA was extracted from the mosquitoes for real-time PCR analysis for yellow fever, chikungunya, mayaro, Zika and dengue viruses. The yellow fever infection rate was 8.2% for Hg. janthinomys (13 mosquitoes), which is the main vector of sylvatic yellow fever in Brazil. In addition to surveying the mosquito fauna of these conservation units, this work demonstrates the importance of monitoring the circulation of viruses near large urban centers.

KEYWORDS: arboviruses; mosquitoes; yellow fever

PMID: 31083286 DOI: 10.3390/insects10050136

Keywords: Arbovirus; Mosquitoes; Yellow fever; Brazil.

——

#RVF Virus and #YellowFever Virus in #Urine: A Potential #Source of #Infection (Virol Sin., summary)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection

Authors: Meng Li, Beibei Wang, Liqiang Li, Gary Wong, Yingxia Liu, Jinmin Ma, Jiandong Li, Hongzhou Lu, Mifang Liang, Ang Li, Xiuqing Zhang, Yuhai Bi, Hui Zeng

Letter / First Online: 19 March 2019

___

Dear Editor,

In recent years, the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased. Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health (Weaver et al.2018). Yellow fever virus (YFV, family Flaviviridae, genus Flavivirus) is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years (Domingo et al. 2018). The most recent large-scale outbreak of YFV occurred in Brazil in which the mortality rate as of February 28, 2018 is 32.78% (WHO 2018). Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is another mosquito-borne virus and primarily circulates in Africa and the Middle East, and in recent years in Europe (Mansfield et al. 2015). During the initial stage of infection, most patients infected with YFV or RVFV present nonspecific symptoms such as fever, headache, and…

(…)

____

Meng Li, Beibei Wang and Liqiang Li have contributed equally to this work.

Electronic supplementary material

The online version of this article ( https://doi.org/10.1007/s12250-019-00096-2) contains supplementary material, which is available to authorized users.

 

Notes

Acknowledgements

This work is supported by grants from the National Science and Technology Major Project of China (2016ZX10004222 and 2016YFC1200800), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010102), Sanming Project of Medicine in Shenzhen (SZSM201412003), Shenzhen Municipal Government of China (JCYJ20160427151920801) and Beijing Municipal Science & Technology Commission (Z161100000116049), and the National Natural Science Foundation of China (NSFC) International Cooperation and Exchange Program (816110193). Y.B. is supported by the NSFC Outstanding Young Scholars (31822055) and Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) (2017122).

 

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

Informed consent was obtained from all patients for the collection and use of all clinical specimens. This article does not contain any studies with animal subjects performed by any of the authors.

Keywords: Flavivirus; Phlebovirus; Yellow Fever; Rift Valley Fever.

——

#Yellowfever virus is susceptible to #sofosbuvir both in vitro and in vivo (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Yellow fever virus is susceptible to sofosbuvir both in vitroand in vivo

Caroline S. de Freitas , Luiza M. Higa , Carolina Q. Sacramento, André C. Ferreira, Patrícia A. Reis, Rodrigo Delvecchio, Fabio L. Monteiro, Giselle Barbosa-Lima, Harrison James Westgarth, Yasmine Rangel Vieira, Mayara Mattos, Natasha Rocha, Lucas Villas Bôas Hoelz,  [ … ], Thiago Moreno L. Souza

Published: January 30, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007072 / This is an uncorrected proof.

 

Abstract

Yellow fever virus (YFV) is a member of the Flaviviridae family. In Brazil, yellow fever (YF) cases have increased dramatically in sylvatic areas neighboring urban zones in the last few years. Because of the high lethality rates associated with infection and absence of any antiviral treatments, it is essential to identify therapeutic options to respond to YFV outbreaks. Repurposing of clinically approved drugs represents the fastest alternative to discover antivirals for public health emergencies. Other Flaviviruses, such as Zika (ZIKV) and dengue (DENV) viruses, are susceptible to sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Our data showed that sofosbuvir docks onto YFV RNA polymerase using conserved amino acid residues for nucleotide binding. This drug inhibited the replication of both vaccine and wild-type strains of YFV on human hepatoma cells, with EC50 values around 5 μM. Sofosbuvir protected YFV-infected neonatal Swiss mice and adult type I interferon receptor knockout mice (A129-/-) from mortality and weight loss. Because of its safety profile in humans and significant antiviral effects in vitro and in mice, Sofosbuvir may represent a novel therapeutic option for the treatment of YF.

Key-words: Yellow fever virus; Yellow fever, antiviral; sofosbuvir

 

Author summary

Yellow fever virus is transmitted by mosquitoes and its infection may be asymptomatic or lead to a wide clinical spectrum ranging from a mild febrile illness to a potentially lethal viral hemorrhagic fever characterized by liver damage. Although a yellow fever vaccine is available, low coverage allows 80,000–200,000 cases and 30,000–60,000 deaths annually worldwide. There are no specific therapy and treatment relies on supportive care, reinforcing an urgent need for antiviral repourposing. Here, we showed that sofosbuvir, clinically approved against hepatitis C, inhibits yellow fever virus replication in liver cell lines and animal models. In vitro, sofosbuvir inhibits viral RNA replication, decreases the number of infected cells and the production of infectious virus particles. These data is particularly relevante since the liver is the main target of yellow fever infection. Sofosbuvir also protected infected animals from mortality, weight loss and liver injury, especially prophylatically. Our pre-clinical results supports a second use of sofosbuvir against yellow fever.

___

Citation: de Freitas CS, Higa LM, Sacramento CQ, Ferreira AC, Reis PA, Delvecchio R, et al. (2019) Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo. PLoS Negl Trop Dis 13(1): e0007072. https://doi.org/10.1371/journal.pntd.0007072

Editor: Samuel V. Scarpino, Northeastern University, UNITED STATES

Received: March 25, 2018; Accepted: December 12, 2018; Published: January 30, 2019

Copyright: © 2019 de Freitas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The financial support was provided by Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ – http://www.faperj.br/ – Grant Number E-26/201.573/2014) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq – http://cnpq.br/ – Grant Numbers 306389/2014-2 and 425636/2016-0). TMLS received the funds. This work has received financial support from the National Institute of Science and Technology in Dengue (INCT dengue), a scheme funded by the Brazilian National Science Council (CNPq, Brazil) and Minas Gerais Foundation for Science (FAPEMIG, Brazil). Funding was also provided by National Council for Scientific and Technological Development (CNPq), Ministry of Science, Technology, Information and Communications (no. 465313/2014-0); Ministry of Education/CAPES (no. 465313/2014-0); Research Foundation of the State of Rio de Janeiro/FAPERJ (no. 465313/2014-0) and Oswaldo Cruz Foundation/FIOCRUZ to National Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDPN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Yellow Fever; Flavivirus; Antivirals; Sofosbuvir; Animal models.

——