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Vaccine-Derived Polioviruses, Central African Republic, 2019.

ABSTRACT: Since May 2019, the Central African Republic has experienced a poliomyelitis outbreak caused by type 2 vaccine-derived polioviruses (VDPV-2s). The outbreak affected Bangui, the capital city, and 10 districts across the country. The outbreak resulted from several independent emergence events of VDPV-2s featuring recombinant genomes with complex mosaic genomes. The low number of mutations (<20) in the viral capsid protein 1-encoding region compared with the vaccine strain suggests that VDPV-2 had been circulating for a relatively short time (probably <3 years) before being isolated. Environmental surveillance, which relies on a limited number of sampling sites in the Central African Republic and does not cover the whole country, failed to detect the circulation of VDPV-2s before some had induced poliomyelitis in children.

SUBMITTER: Joffret ML

PROVIDER: S-EPMC7853572 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Vaccine-derived polioviruses (VDPVs) have caused poliomyelitis outbreaks in communities with sub-optimal vaccination. Israeli environmental surveillance of sewage from populations with high (>95%) documented vaccine coverage of confirmed efficacy identified two separate evolutionary clusters of VDPVs: Group 1 (1998-2005, one system, population 1.6x10(6)) and Group 2 (2006, 2 systems, populations 0.7x10(6) and 5x10(4)). PRINCIPAL FINDINGS: Molecular analyses support evolution of nine Group 1 VDPVs along five different lineages, starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1 recombinant strain, and independent evolution of three Group 2 VDPVs along one lineage starting from a different recombinant strain. The primary evidence for two independent origins was based on comparison of unique recombination fingerprints, the number and distribution of identical substitutions, and evolutionary rates. Geometric mean titers of neutralizing antibodies against Group 1 VDPVs were significantly lower than against vaccine strains in all age-group cohorts tested. All individuals had neutralizing titers >1:8 against these VDPVs except 7% of the 20-50 year cohort. Group 1 VDPVs were highly neurovirulent in a transgenic mouse model. Intermediate levels of protective immunity against Group 2 VDPVs correlated with fewer (5.0+1.0) amino acid substitutions in neutralizing antigenic sites than in Group 1 VDPV's (12.1+/-1.5). SIGNIFICANCE: VDPVs that revert from live oral attenuated vaccines and reacquire characteristics of wild-type polioviruses not only threaten populations with poor immune coverage, but are also a potential source for re-introduction of poliomyelitis into highly immune populations through older individuals with waning immunity. The presence of two independently evolved groups of VDPVs in Israel and the growing number of reports of environmental VDPV elsewhere make it imperative to determine the global frequency of environmental VDPV. Our study underscores the importance of the environmental surveillance and the need to reconsider the global strategies for polio eradication and the proposed cessation of vaccination.

Project description:Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5'-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5'UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpol region. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.

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Vaccine-Derived Polioviruses, Central African Republic, 2019.

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