Epidemic viral reemergence : coxsackievirus A6 et entérovirus A71, from hand foot and mouth disease to neurologic complications

Les entérovirus (EV) sont des virus entériques (famille des Picornaviridae) classés parmi quatre espèces taxonomiques (A à D). Les infections à EV symptomatiques sont associées à des atteintes neurologiques, respiratoires, cardiaques, musculaires, cutanéomuqueuses. La maladie pieds-mains-bouche (PMB) se caractérise par une éruption cutanée et des ulcérations buccales chez les enfants de moins 5 ans. L’EVA71 (EVA71) et le coxsackievirus A6 (CVA6) sont parmi les types d’EV de l’espèce A, les plus fréquemment associés à la maladie PMB. En France, l’EVA71 est associé à la recrudescence d’atteintes neurologiques depuis 2016, et le CVA6 est relié à la survenue d’épidémies régulières de maladie PMB. L’objectif de la thèse est de comparer les réémergences épidémiques de ces deux virus par l’analyse comparative des génomes. L’épidémie d’atteintes neurologiques sévères en 2016 a été associée au variant C1v2015 classé dans le sous-génogroupe C1 d’EVA71 et dont l’émergence a été datée en 2010. Le génome de ce virus présente une structure chimérique caractéristique de multiples évènements de recombinaison. Le génome du virus C1v2015 montre des variations notables par rapport à celui des virus antérieurs dans des segments codant des épitopes exposés à la surface des protéines de capside. Nous avons daté en 2013 la survenue d’un évènement de recombinaison qui a remplacé le gène de la polymérase 3Dpol précédant de peu la propagation épidémique du virus en Europe à partir de 2015. Pour étudier le CVA6, nous avons mis au point une méthode de séquençage NGS que nous avons appliquée à des échantillons cliniques recueillis en France entre 2010 et 2018. En France, depuis 2014, les épidémies sont liées au sous-génogroupe D4 qui a émergé globalement en 2004. L’étude du gène 3Dpol permet d’identifier 5 nouvelles formes recombinantes. Les caractéristiques épidémio-cliniques des cas de maladie PMB rapportés en France montrent que l’émergence du CVA6 a été contemporaine de l’augmentation de formes atypiques de la maladie, une tendance aussi observée à l’échelle mondiale. En conclusion, nos travaux montrent l’intérêt de l’analyse des génomes complets d’EV pour comparer les variations moléculaires et retracer l’histoire évolutive et épidémique des virus réémergents.Enteroviruses (EVs) are enteric viruses assigned to the Picornaviridae family and classified into four taxonomic species (A to D). Symptomatic EV infections can be associated with diseases of the nervous system, lung, heart, muscle, and skin. Hand-foot-and-mouth disease (HFMD) is characterized by a rash and oral ulcerations in children under 5 years. Enterovirus A71 (EVA71) and coxsackievirus A6 (CVA6) are the two most frequent EV types of species A reported in HFMD cases. In France, EVA71 was associated with an increasing number of neurological diseases since 2016, and CVA6 was associated with regular HFMD outbreaks. The main aim of the thesis is to investigate and compare the epidemic reemergences of these two viruses by using whole-genome analysis. The outbreak of neurological diseases in 2016 was associated with the virus C1v2015 assigned to the EVA71 subgenogroup C1, which emerged in 2010. This virus has a chimeric genome characterized by multiple recombination events. Compared with the genomes of the earlier C1 viruses, the C1v2015 genome displays characteristic changes within epitopes exposed at the capsid surface. The recombination event that changed in 2013 the 3Dpol gene occurred shortly before the epidemic spread in Europe in 2015. To investigate CVA6, we designed a whole-genome amplification technique and used high throughput sequencing to determine viral genomes in buccal specimens collected in France between 2010 and 2018. We did not find major variations in structural genes, but we identified five recombinant forms not previously reported by the study of the 3Dpol gene. Paralleling the worldwide shifts, the clinical and epidemiological features of HFMD cases reported in France indicated the epidemic reemergence of CVA6 was contemporaneous of the increasing frequency of an atypical disease. To conclude, our data highlight the value of whole-genome analysis to compare molecular variations and trace the evolutionary and epidemic histories of reemerging enteroviruses

Réémergence virale épidémique : coxsackievirus A6 et entérovirus A71, de la maladie pied-main-bouche aux atteintes neurologiques

Enteroviruses (EVs) are enteric viruses assigned to the Picornaviridae family and classified into four taxonomic species (A to D). Symptomatic EV infections can be associated with diseases of the nervous system, lung, heart, muscle, and skin. Hand-foot-and-mouth disease (HFMD) is characterized by a rash and oral ulcerations in children under 5 years. Enterovirus A71 (EVA71) and coxsackievirus A6 (CVA6) are the two most frequent EV types of species A reported in HFMD cases. In France, EVA71 was associated with an increasing number of neurological diseases since 2016, and CVA6 was associated with regular HFMD outbreaks. The main aim of the thesis is to investigate and compare the epidemic reemergences of these two viruses by using whole-genome analysis. The outbreak of neurological diseases in 2016 was associated with the virus C1v2015 assigned to the EVA71 subgenogroup C1, which emerged in 2010. This virus has a chimeric genome characterized by multiple recombination events. Compared with the genomes of the earlier C1 viruses, the C1v2015 genome displays characteristic changes within epitopes exposed at the capsid surface. The recombination event that changed in 2013 the 3Dpol gene occurred shortly before the epidemic spread in Europe in 2015. To investigate CVA6, we designed a whole-genome amplification technique and used high throughput sequencing to determine viral genomes in buccal specimens collected in France between 2010 and 2018. We did not find major variations in structural genes, but we identified five recombinant forms not previously reported by the study of the 3Dpol gene. Paralleling the worldwide shifts, the clinical and epidemiological features of HFMD cases reported in France indicated the epidemic reemergence of CVA6 was contemporaneous of the increasing frequency of an atypical disease. To conclude, our data highlight the value of whole-genome analysis to compare molecular variations and trace the evolutionary and epidemic histories of reemerging enteroviruses.Les entérovirus (EV) sont des virus entériques (famille des Picornaviridae) classés parmi quatre espèces taxonomiques (A à D). Les infections à EV symptomatiques sont associées à des atteintes neurologiques, respiratoires, cardiaques, musculaires, cutanéomuqueuses. La maladie pieds-mains-bouche (PMB) se caractérise par une éruption cutanée et des ulcérations buccales chez les enfants de moins 5 ans. L’EVA71 (EVA71) et le coxsackievirus A6 (CVA6) sont parmi les types d’EV de l’espèce A, les plus fréquemment associés à la maladie PMB. En France, l’EVA71 est associé à la recrudescence d’atteintes neurologiques depuis 2016, et le CVA6 est relié à la survenue d’épidémies régulières de maladie PMB. L’objectif de la thèse est de comparer les réémergences épidémiques de ces deux virus par l’analyse comparative des génomes. L’épidémie d’atteintes neurologiques sévères en 2016 a été associée au variant C1v2015 classé dans le sous-génogroupe C1 d’EVA71 et dont l’émergence a été datée en 2010. Le génome de ce virus présente une structure chimérique caractéristique de multiples évènements de recombinaison. Le génome du virus C1v2015 montre des variations notables par rapport à celui des virus antérieurs dans des segments codant des épitopes exposés à la surface des protéines de capside. Nous avons daté en 2013 la survenue d’un évènement de recombinaison qui a remplacé le gène de la polymérase 3Dpol précédant de peu la propagation épidémique du virus en Europe à partir de 2015. Pour étudier le CVA6, nous avons mis au point une méthode de séquençage NGS que nous avons appliquée à des échantillons cliniques recueillis en France entre 2010 et 2018. En France, depuis 2014, les épidémies sont liées au sous-génogroupe D4 qui a émergé globalement en 2004. L’étude du gène 3Dpol permet d’identifier 5 nouvelles formes recombinantes. Les caractéristiques épidémio-cliniques des cas de maladie PMB rapportés en France montrent que l’émergence du CVA6 a été contemporaine de l’augmentation de formes atypiques de la maladie, une tendance aussi observée à l’échelle mondiale. En conclusion, nos travaux montrent l’intérêt de l’analyse des génomes complets d’EV pour comparer les variations moléculaires et retracer l’histoire évolutive et épidémique des virus réémergents

Réémergence virale épidémique : coxsackievirus A6 et entérovirus A71, de la maladie pied-main-bouche aux atteintes neurologiques

Enteroviruses (EVs) are enteric viruses assigned to the Picornaviridae family and classified into four taxonomic species (A to D). Symptomatic EV infections can be associated with diseases of the nervous system, lung, heart, muscle, and skin. Hand-foot-and-mouth disease (HFMD) is characterized by a rash and oral ulcerations in children under 5 years. Enterovirus A71 (EVA71) and coxsackievirus A6 (CVA6) are the two most frequent EV types of species A reported in HFMD cases. In France, EVA71 was associated with an increasing number of neurological diseases since 2016, and CVA6 was associated with regular HFMD outbreaks. The main aim of the thesis is to investigate and compare the epidemic reemergences of these two viruses by using whole-genome analysis. The outbreak of neurological diseases in 2016 was associated with the virus C1v2015 assigned to the EVA71 subgenogroup C1, which emerged in 2010. This virus has a chimeric genome characterized by multiple recombination events. Compared with the genomes of the earlier C1 viruses, the C1v2015 genome displays characteristic changes within epitopes exposed at the capsid surface. The recombination event that changed in 2013 the 3Dpol gene occurred shortly before the epidemic spread in Europe in 2015. To investigate CVA6, we designed a whole-genome amplification technique and used high throughput sequencing to determine viral genomes in buccal specimens collected in France between 2010 and 2018. We did not find major variations in structural genes, but we identified five recombinant forms not previously reported by the study of the 3Dpol gene. Paralleling the worldwide shifts, the clinical and epidemiological features of HFMD cases reported in France indicated the epidemic reemergence of CVA6 was contemporaneous of the increasing frequency of an atypical disease. To conclude, our data highlight the value of whole-genome analysis to compare molecular variations and trace the evolutionary and epidemic histories of reemerging enteroviruses.Les entérovirus (EV) sont des virus entériques (famille des Picornaviridae) classés parmi quatre espèces taxonomiques (A à D). Les infections à EV symptomatiques sont associées à des atteintes neurologiques, respiratoires, cardiaques, musculaires, cutanéomuqueuses. La maladie pieds-mains-bouche (PMB) se caractérise par une éruption cutanée et des ulcérations buccales chez les enfants de moins 5 ans. L’EVA71 (EVA71) et le coxsackievirus A6 (CVA6) sont parmi les types d’EV de l’espèce A, les plus fréquemment associés à la maladie PMB. En France, l’EVA71 est associé à la recrudescence d’atteintes neurologiques depuis 2016, et le CVA6 est relié à la survenue d’épidémies régulières de maladie PMB. L’objectif de la thèse est de comparer les réémergences épidémiques de ces deux virus par l’analyse comparative des génomes. L’épidémie d’atteintes neurologiques sévères en 2016 a été associée au variant C1v2015 classé dans le sous-génogroupe C1 d’EVA71 et dont l’émergence a été datée en 2010. Le génome de ce virus présente une structure chimérique caractéristique de multiples évènements de recombinaison. Le génome du virus C1v2015 montre des variations notables par rapport à celui des virus antérieurs dans des segments codant des épitopes exposés à la surface des protéines de capside. Nous avons daté en 2013 la survenue d’un évènement de recombinaison qui a remplacé le gène de la polymérase 3Dpol précédant de peu la propagation épidémique du virus en Europe à partir de 2015. Pour étudier le CVA6, nous avons mis au point une méthode de séquençage NGS que nous avons appliquée à des échantillons cliniques recueillis en France entre 2010 et 2018. En France, depuis 2014, les épidémies sont liées au sous-génogroupe D4 qui a émergé globalement en 2004. L’étude du gène 3Dpol permet d’identifier 5 nouvelles formes recombinantes. Les caractéristiques épidémio-cliniques des cas de maladie PMB rapportés en France montrent que l’émergence du CVA6 a été contemporaine de l’augmentation de formes atypiques de la maladie, une tendance aussi observée à l’échelle mondiale. En conclusion, nos travaux montrent l’intérêt de l’analyse des génomes complets d’EV pour comparer les variations moléculaires et retracer l’histoire évolutive et épidémique des virus réémergents

Rotavirus in various animal species in Ouagadougou, Burkina Faso: detection of genotype G9.

Objectives: Rotaviruses have a wide host range, infecting many animal species as well as humans. The segmented nature of the genome suggests that rotaviruses are able to form new strains by a mechanism of reassortment. Animal rotaviruses are regarded as a potential reservoir for genetic diversity of human rotaviruses. The aim of this study was to determine the incidence and molecular characteristics of rotavirus in various healthy animals in Ouagadougou, Burkina Faso.Methodology and results: A total of 618 faeces samples from various animal species with different living environments were collected between June 2009 and August 2011, and analyzed for rotavirus group A antigen detection by immunochromatographic test (SD Bioline Rota/Adeno®; Standard diagnostics, Inc., Korea). A second sample collection between February and March 2015 involved only farm animals (n= 138) and analyzed for rotavirus group A antigen detection by ELISA test (Ridascreen®, R-Biopharm AG, Darmstadt Germany). The rotaviruses antigen-positives samples for ELISA were further confirmed and characterized by reversetranscription (RT-PCR). For immunochromatographic detection, the prevalence of rotavirus A and adenovirus antigens were found in 7.4% of pig, 31% of poultry, 33.4% of pigeon, 35.7% of rabbit, 46-58% in bovine, 13.8% of shrimps, 14.8% of snails and 28.6% of captain (Lates niloticus). The detection of rotavirus antigen by ELISA reported rates of 7.4% in pigs, 4.1% in cattle and 14.3% in poultry and no case of rotavirus was detected in sheep. The molecular characterization of the strains established that they belong to the G9 genotype (3/ 7; 42.9%).Conclusion and application of results: This study provides evidence asymptomatic hosts of rotavirus. This study report for the first time rotaviruses detection and presence of the emerged genotype G9 in farms animals in Burkina Faso. These results justify the need to monitoring animals’ rotaviruses in Burkina Faso.Keywords: Rotavirus group A, Animals, molecular characterization, Burkina Faso

Temporal distribution of gastroenteritis viruses in Ouagadougou, Burkina Faso: seasonality of rotavirus

Abstract Background Acute gastroenteritis is one of the most common diseases among children and adults, and continues to cause a major problem of public health in Burkina Faso. The temporal pattern of rotavirus, norovirus, sapovirus, astrovirus, adenovirus and Aichivirus A was studied by examining prevalence of gastroenteritis viruses in association with meteorological variables in Ouagadougou, Burkina Faso. Methods Stool samples from 263 children under 5 years of age and 170 older children patients, adolescent and adults with gastroenteritis were collected in Ouagadougou, Burkina Faso from November 2011 to September 2012. Enteric viruses were detected using real-time or end-point (RT-) PCR. Temperature, humidity and monthly rainfall were recorded from the National Meteorological Direction. Categorical data were compared by Chi-square tests and the effect of weather variables and monthly prevalence were analyzed using Pearson Correlation Coefficient test. Results The prevalence of rotavirus infections was significantly higher in the dry season (Season S1) compared to the wet season (season S2) (p = 0.03) among the population of children under 5 years of age. No statistically significant difference was observed regarding other gastroenteritis viruses comparing the dry season and the wet season. Positive cases of rotavirus, norovirus, adenovirus and sapovirus in children under 5 years of age were correlated with temperature (r = −0.68, p = 0.01; r = −0.74, p < 0.001; r = −0.68, p = 0.01; r = −0.65, p = 0.02, respectively) and only rotavirus, adenovirus and astrovirus were correlated with relative humidity (r = −0.61, p = 0.04; r = −0.54, p = 0.08; r = −0.51, p = 0.1 respectively). No correlation was observed with rainfall. In older children, adolescent and adults patients, rotavirus and norovirus correlated with relative humidity (r = −0.58, p = 0.05; r = 0.54, p = 0.08 respectively), but, no correlation was observed between the temperature and the rainfall. Conclusion This study extends knowledge on the monthly fluctuations on the prevalence of viral gastroenteritis. These results can provide valuable information necessary to alert health care providers when a period of infection in the community is likely to occur. The transmission of these viruses in Burkina Faso could depends on multiple factors including climatic variables

Coxsackievirus A6 Recombinant Subclades D3/A and D3/H Were Predominant in Hand-Foot-And-Mouth Disease Outbreaks in the Paediatric Population, France, 2010–2018

International audienceCoxsackievirus A6 (CVA6) emerged as the most common enterovirus of seasonal outbreaks of hand-foot-and-mouth disease (HFMD). We investigated CVA6 genetic diversity among the clinical phenotypes reported in the paediatric population during sentinel surveillance in France between 2010 and 2018. CVA6 infection was confirmed in 981 children (mean age 1.52 years [IQR 1.17–2.72]) of whom 564 (58%) were males. Atypical HFMD was reported in 705 (72%) children, followed by typical HFMD in 214 (22%) and herpangina in 57 (6%) children. Throat specimens of 245 children were processed with a target-enrichment new-generation sequencing approach, which generated 213 complete CVA6 genomes. The genomes grouped within the D1 and D3 clades (phylogeny inferred with the P1 genomic region). In total, 201 genomes were classified among the recombinant forms (RFs) A, B, F, G, H, and N, and 12 genomes were assigned to 5 previously unreported RFs (R–V). The most frequent RFs were A (58%), H (19%), G (6.1%), and F (5.2%). The yearly number of RFs ranged between 1 (in 2012 and 2013) and 6 (2018). The worldwide CVA6 epidemic transmission began between 2005 and 2007, which coincided with the global spread of the recombinant subclade D3/RF-A

Multirecombinant Enterovirus A71 Subgenogroup C1 Isolates Associated with Neurologic Disease, France, 2016–2017

International audienceIn 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children