Autochthonous Japanese Encephalitis with Yellow Fever Coinfection in Africa

Simon‐Lorière, Etienne; Faye, Ousmane; Prot, Matthieu; Casadémont, Isabelle; Fall, Gamou; Fernandez-Garcia, Maria Dolores; Diagne, Moussa Moïse; Kipela, Jean-Marie; Fall, Ibrahima Socé; Holmes, Edward C.; Sakuntabhai, Anavaj; Sall, Amadou Alpha

doi:10.1056/nejmc1701600

Cited by 105 publications

(72 citation statements)

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“…In this study, untargeted NGS has proved a useful tool when applied retrospectively to screen for coinfecting viruses that are not investigated in www.nature.com/scientificreports www.nature.com/scientificreports/ routine laboratory work. In recent years, NGS has boosted identification of unsuspected and novel viruses and is becoming the standard for the discovery of viral pathogens 33,34 . It has been successfully used to identify or characterize full-genomes of new HPeVs like a HPeV1 variant 35 , type 4 31 , types 5 and 6 32 , type 7 36 , type 16 26 , type 17 37 , types 18 and 19 38 or to detect HPeVs in clinical specimens 25,26,[39][40][41] .…”

Section: Discussionmentioning

confidence: 99%

Identification and molecular characterization of the first complete genome sequence of Human Parechovirus type 15

Fernandez-Garcia

Simon‐Lorière

Kébé

et al. 2020

Sci Rep

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Using a metagenomics approach, we have determined the first full-length genome sequence of a human parechovirus type 15 (HPeV15) strain, isolated from a child with acute flaccid paralysis and co-infected with EV-A71. HPeV15 is a rarely reported type. To date, no full-length genome sequence of HPeV15 is available in the GenBank database, where only limited VP1 sequences of this virus are available. Pairwise comparisons of the complete VP1 nucleotide and deduced amino acid sequences revealed that the study strain belongs to type 15 as it displayed 79.6% nucleotide and 93.4% amino acid identity with the HPeV15 prototype strain. Comparative analysis of available genomic regions and phylogenetic analysis using the P2 and P3 coding regions revealed low nucleotide identity to HPeV reference genomes. Phylogenetic and similarity plot analyses showed that genomic recombination events might have occurred in the UTRs and nonstructural region during HPeV15 evolution. The study strain has high similarity features with different variants of HPeV3 suggesting intertypic recombination. Our data contributes to the scarce data available on HPeVs in Africa and provides valuable information for future studies that aim to understand the evolutionary history, molecular epidemiology or biological and pathogenic properties of HPeV15. Human parechoviruses (HPeVs) are non-enveloped viruses that belong to one of the four species of genus Parechovirus within the Picornaviridae family. HPeV positive-sense single-stranded RNA genome is about 7300 bases in length, flanked by 5′ and 3′ untranslated regions (UTRs). The genome encodes a polyprotein which is cleaved by the viral protease (3 C) to produce the mature structural (VP0, VP3 and VP1) and nonstructural (2A-C, 3A-D) proteins 1. HPeVs can be transmitted through the fecal-oral and respiratory routes 1,2. HPeV infections are common throughout the world and most often cause asymptomatic or mild gastrointestinal or respiratory symptoms 1,2. However, syndromes such as encephalitis, aseptic meningitis, acute flaccid paralysis (AFP), sepsis and myocarditis have been increasingly recognized in primary HPeV infection in neonates and infants 2. After EVs, HPeVs are considered the second most common cause of central nervous system (CNS) viral infections 2. However, HPeV infections are currently underdiagnosed given that routine diagnostic assays are generally lacking in clinical settings 1,3. Following HPeV intestinal replication, infectious viruses are shed in feces where viruses can be detected by PCR and virus isolation 3. However, HPeVs are known for poor adaptation to cell cultivation systems and not all types replicate in cell lines routinely used for enterovirus (EV) detection 4,5. Because specific types could be missed or underdiagnosed using viral isolation, molecular identification methods are highly recommended for the routine detection of HPeVs in clinical samples 3,4. To date, 19 different HPeV types (HPeV1 to 19) have been described based on sequence similarity within their VP1 capsid pro...

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Section: Discussionmentioning

confidence: 99%

Identification and molecular characterization of the first complete genome sequence of Human Parechovirus type 15

Fernandez-Garcia

Simon‐Lorière

Kébé

et al. 2020

Sci Rep

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“…Certain flaviviruses such as DENV, WNV and most recently ZIKV are (re-)emerging in new areas (1–3). Some evidence suggests the first autochthonous transmission of JEV in Africa (4).…”

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confidence: 99%

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

Mishra

Boudewijns

Schmid

et al. 2019

Preprint

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ABSTRACTRecent massive outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being not prepared against future YFV epidemics. Here we report that a live-attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev® that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific non-neutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV non-structural (NS) proteins. Our findings reveal the importance of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev® can confer protection against two flaviviruses. This dual protection has implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev® may already be protected against YFV should outbreaks ever occur on that continent as feared by WHO.IMPORTANCEEfficient and safe vaccines exist against yellow fever (e.g. YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses. However, vaccine supply cannot cope with an increasing demand posed by massive urban outbreaks in recent years. Here we report that JE-CVax/Imojev®, a YFV-17D-based chimeric Japanese encephalitis vaccine also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev® may be considered. Moreover, wider use of JE-CVax/Imojev® in Asia may lower the risk of the much-feared YFV spill over to the continent. More in general chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses can be considered dual vaccines, for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection [inherent to current dengue vaccines and dengue vaccine candidates] could be designed.

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“…This increases the risk of JEV global emergence despite the fact that there is a JE vaccine. It remains to be seen whether or not the first detection of JEV genomic sequence in a human in Africa [112] reflects the early stages of JEV emergence in this country.…”

Section: Discussionmentioning

confidence: 99%

“…tritaeniorhynchous the primary vector of JEV was recently identified in north western Greece [111] thus potentially increasing the risk of JEV emergence in Europe. Indeed, the even more recent detection of autochthonous co-infections of a human by both YFV and JEV in Angola [112], lends support to the idea that JEV may already have broken free of its apparent Asian boundaries.…”

Section: Emergence Of Culex-species Associated Flavivirusesmentioning

confidence: 94%

Emerging arboviruses: Why today?

et al. 2017

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The recent global (re)emergence of arthropod-borne viruses (arboviruses), such as chikungunya and Zika virus, was widely reported in the media as though it was a new phenomenon. This is not the case. Arboviruses and other human microbial pathogens have been (re)emerging for centuries. The major difference today is that arbovirus emergence and dispersion are more rapid and geographically extensive, largely due to intensive growth of global transportation systems, arthropod adaptation to increasing urbanisation, our failure to contain mosquito population density increases and land perturbation. Here we select examples of (re)emerging pathogenic arboviruses and explain the reasons for their emergence and different patterns of dispersal, focusing particularly on the mosquito vectors which are important determinants of arbovirus emergence. We also attempt to identify arboviruses likely to (re)emerge in the future.

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Autochthonous Japanese Encephalitis with Yellow Fever Coinfection in Africa

Cited by 105 publications

References 4 publications

Identification and molecular characterization of the first complete genome sequence of Human Parechovirus type 15

Identification and molecular characterization of the first complete genome sequence of Human Parechovirus type 15

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

Emerging arboviruses: Why today?

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