Reemergence of Recombinant Vaccine–derived Polioviruses in Healthy Children, Madagascar

International audiencePoliomyelitis outbreaks caused by pathogenic vaccine-derived polioviruses (VDPVs) are primarily a result of low polio vaccine coverage. Low coverage enables interhuman circulation of polioviruses (PVs) from the oral polio vaccine (OPV), and it enables genetic drift of the viruses and their subsequent reversion to neurovirulent phenotypes. Polio outbreaks associated with type 2 or 3 VDPVs (VDPV2s or VDPV3s) were reported in 2001-2002 and 2005 in Toliara Province in southern Madagascar. These VDPVs were found in patients with acute flaccid paralysis (AFP) and in healthy children who were contacts of the patients with AFP. The genomes of these VDPVs belong to several independent, complex mosaic recombinant lineages composed of sequences derived from vaccine polioviruses and other co-circulating species C human enteroviruses (human EV-C). The 2001-2002 and 2005 outbreaks in Toliara Province were stopped after rapid and efficient OPV vaccination campaigns

High permissiveness for genetic exchanges between enteroviruses of species A, including enterovirus 71, favours evolution through intertypic recombination in Madagascar

International audienceHuman enteroviruses of species A (EV-A) are the leading cause of hand-foot-and-mouth disease (HFMD). EV-A71 is frequently implicated in HFMD outbreaks and can also cause severe neurological manifestations. We investigated the molecular epidemiological processes at work and the contribution of genetic recombination to the evolutionary history of EV-A in Madagascar, focusing on the recently described EV-A71 genogroup F in particular. Twenty-three EV-A isolates, collected mostly in 2011 from healthy children living in various districts of Madagascar, were characterized by whole-genome sequencing. Eight different types were identified, highlighting the local circulation and diversity of EV-A. Comparative genome analysis revealed evidence of frequent recent intra- and intertypic genetic exchanges between the noncapsid sequences of Madagascan EV-A isolates. The three EV-A71 isolates had different evolutionary histories in terms of recombination, with one isolate displaying a mosaic genome resulting from recent genetic exchanges with Madagascan coxsackieviruses A7 and possibly A5 and A10 or common ancestors. The engineering and characterization of recombinants generated from progenitors belonging to different EV-A types or EV-A71 genogroups with distantly related nonstructural sequences indicated a high level of permissiveness for intertypic genetic exchange in EV-A. This permissiveness suggests that the primary viral functions associated with the nonstructural sequences have been highly conserved through the diversification and evolution of the EV-A species. No outbreak of disease due to EV-A has yet been reported in Madagascar, but the diversity, circulation, and evolution of these viruses justify surveillance of EV-A circulation and HFMD cases to prevent possible outbreaks due to emerging strains.IMPORTANCE Human enteroviruses of species A (EV-A), including EV-A71, are the leading cause of hand-foot-and-mouth disease (HFMD) and may also cause severe neurological manifestations. We investigated the circulation and molecular evolution of EV-A in Madagascar, focusing particularly on the recently described EV-A71 genogroup F. Eight different types, collected mostly in 2011, were identified, highlighting the local circulation and diversity of EV-A. Comparative genome analysis revealed evidence of frequent genetic exchanges between the different types of isolates. The three EV-A71 isolates had different evolutionary histories in terms of recombination. The engineering and characterization of recombinants involving progenitors belonging to different EV-A types indicated a high degree of permissiveness for genetic exchange in EV-A. No outbreak of disease due to EV-A has yet been reported in Madagascar, but the diversity, circulation, and evolution of these viruses justify the surveillance of EV-A circulation to prevent possible HFMD outbreaks due to emerging strains

Reemergence of recombinant vaccine-derived poliovirus outbreak in Madagascar.

International audienceBACKGROUND: After the 2001-2002 poliomyelitis outbreak due to recombinant vaccine-derived polioviruses (VDPVs) in the Toliara province of Madagascar, another outbreak reoccurred in the same province in 2005. METHODS: We conducted epidemiological and virological investigations for each polio case patient and for their contacts. RESULTS: From May to August 2005, a total of 5 cases of acute flaccid paralysis were reported among unvaccinated or partially vaccinated children 2-3 years old. Type-3 or type-2 VDPV was isolated from case patients and from healthy contacts. These strains were classified into 4 recombinant lineages that showed complex mosaic genomic structures originating from different vaccine strain serotypes and probably from human enterovirus C (HEV-C) species. Genetic relatedness could be observed among these 4 lineages. Vaccination coverage of the population was very low (<50%). CONCLUSIONS: The broad distribution of VDPVs in the province and their close genetic relationship indicate intense and rapid cocirculation and coevolution of the vaccine strains and of their related HEV-C strains. The occurrence of an outbreak due to VDPV 3 years after a previous outbreak indicates that a short period with low vaccination coverage is enough to create favorable conditions for the emergence of VDPV in this setting

Additional file 2 of Enterovirus detection in different regions of Madagascar reveals a higher abundance of enteroviruses of species C in areas where several outbreaks of vaccine-derived polioviruses occurred

Additional file 2: Figure S1. Detection of NPEVs on RD and HEp-2c cells

Additional file 3 of Enterovirus detection in different regions of Madagascar reveals a higher abundance of enteroviruses of species C in areas where several outbreaks of vaccine-derived polioviruses occurred

Additional file 3: Figure S2. Phylogenetic trees of Madagascan EV-Cs based on the 5′UTR, the VP1- and the 3D-encoding sequences. The isolates are colour-coded according to their respective type; triangles indicate isolates from this study, circles isolates from previous works

Additional file 1 of Enterovirus detection in different regions of Madagascar reveals a higher abundance of enteroviruses of species C in areas where several outbreaks of vaccine-derived polioviruses occurred

Additional file 1: Table S1. Accession numbers of the sequences used to draw the tree displayed in Fig. 7