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Reemergence of recombinant vaccine-derived polioviruses in healthy children, Madagascar.

Razafindratsimandresy R, Joffret ML, Rabemanantsoa S, Andriamamonjy S, Heraud JM, Delpeyroux F - Emerging Infect. Dis. (2013)

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Poliomyelitis outbreaks caused by pathogenic vaccine-derived polioviruses (VDPVs) are primarily a result of low polio vaccine coverage... 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... Sample extracts were used to inoculate human RD and HEp-2c cells and mouse L cells expressing the human poliovirus cellular receptor CD155 (L20B cells)... Of the 616 samples, 238 induced cytopathogenic effects in human cells, of which 20 also induced cytopathogenic effects in L20B cells; the latter samples were confirmed by reverse transcription PCR molecular testing to contain PV strains... All PV isolates originated from children who had not received OPV in the 30 days before samples were collected... We sequenced the genomic regions encoding the capsid viral protein (VP1) of the 20 isolates confirmed to contain PV strains: 3 type 2 PV isolates showed >0.5% nt sequence divergence from the type 2 OPV strain (Sabin 2) and were thus identified as potentially pathogenic VDPV2s... Almost complete genomic sequencing, from nt 36 to nt 7,420 (Sabin 2 numbering), was subsequently performed (EMBL accession nos... HF913426– HF913428)... No polio cases have been reported in the province since then, suggesting that VDPV circulation was limited or stopped by these campaigns... Massive OPV immunization campaigns worldwide have greatly decreased the frequency of poliomyelitis caused by wild-type PVs... However, after the disease has been eliminated in developing countries, low polio vaccine coverage frequently enables the emergence of VDPVs or the reintroduction of wild-type PV from disease-endemic countries; both scenarios threaten the success of the poliomyelitis eradication program... More than 640 polio cases caused by circulating VDPVs have been reported in 21 developing countries... We have shown that even in the absence of polio cases, potentially pathogenic circulating VDPVs can be detected in fecal samples collected from children living in areas with fluctuating and often low polio vaccine coverage... In Madagascar, vaccination appears to have cleared emerging VDPVs and to have prevented polio cases in children.

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Phylogenetic trees showing genetic relationships between sequences of vaccine-derived poliovirus (VDPV) isolates. The trees are based on nucleotide sequence alignments of various subgenomic regions. Multiple sequence alignments were performed with CLC Main Workbench 5.7.2 software (CLC bio, Aarhus, Denmark). Phylograms were constructed with MEGA 4 (http://megasoftware.net/mega4/mega.html), using the Jukes-Cantor algorithm for genetic distance determination and the neighbor-joining method. The robustness of the resulting trees was assessed with 1,000 bootstrap replications. A) Tree built from 712-bp fragments of the 5′–untranslated region (nt 36–747, with reference to Sabin 2 nucleotide numbering). B) Tree built from 2,637-bp fragments of the P1 region (nt 748–3,384). C) Tree built from 1,725-bp fragments of the P2 region (nt 3,385–5,109). D) Tree built from 2,259-bp fragments of the P3 region (nt 5,110–7,368). Names (isolate name-accession no.) are VDPV isolates recovered in Madagascar in 2011, 2005, and 2001–2002. Sequences of other isolates (CV-A11, 13, and 17) from Madagascar were also used. The percentage of bootstrap replicates is indicated at nodes if >70%. The length of branches is proportional to the number of nucleotide differences (percent divergence).Scale bars indicate genetic distances.
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Figure 1: Phylogenetic trees showing genetic relationships between sequences of vaccine-derived poliovirus (VDPV) isolates. The trees are based on nucleotide sequence alignments of various subgenomic regions. Multiple sequence alignments were performed with CLC Main Workbench 5.7.2 software (CLC bio, Aarhus, Denmark). Phylograms were constructed with MEGA 4 (http://megasoftware.net/mega4/mega.html), using the Jukes-Cantor algorithm for genetic distance determination and the neighbor-joining method. The robustness of the resulting trees was assessed with 1,000 bootstrap replications. A) Tree built from 712-bp fragments of the 5′–untranslated region (nt 36–747, with reference to Sabin 2 nucleotide numbering). B) Tree built from 2,637-bp fragments of the P1 region (nt 748–3,384). C) Tree built from 1,725-bp fragments of the P2 region (nt 3,385–5,109). D) Tree built from 2,259-bp fragments of the P3 region (nt 5,110–7,368). Names (isolate name-accession no.) are VDPV isolates recovered in Madagascar in 2011, 2005, and 2001–2002. Sequences of other isolates (CV-A11, 13, and 17) from Madagascar were also used. The percentage of bootstrap replicates is indicated at nodes if >70%. The length of branches is proportional to the number of nucleotide differences (percent divergence).Scale bars indicate genetic distances.

Mentions: Isolate MAD-2675–11 was shown to be a mutated Sabin 2 PV, but isolates MAD-2593–11 and MAD-2642–11 displayed mosaic recombinant genomes composed of sequences derived from Sabin 2 and other human EV-Cs. Both recombinants had the 5′–untranslated region (UTR), the nonstructural P2–P3 regions, and the 3′-UTR derived from non-PV human EV-C. The 2 recombination sites were similarly located in each of these recombinant genomes (approximately at nt 760 and nt 3,368) at the 2 extremities of the structural genomic P1 region. Although these recombinants appeared to be related, they had different non-PV human EV-C sequences in the P2–P3 region and the 3′-UTR (6.0%–20.0% nt sequence difference). The phylogenetic relationship of these isolates to the previous Madagascar VDPV2s was assessed: the 2011 isolates originated from 2 novel, independent events (Figure). The 2011 VDPVs had lost the major attenuating determinants in the 5′-UTR (guanine to adenine at nt 481) and VP1 region (isoleucine to threonine at codon 143) regions (8). This finding strongly suggests that the 2011 VDPVs had regained a degree of neurovirulence.


Reemergence of recombinant vaccine-derived polioviruses in healthy children, Madagascar.

Razafindratsimandresy R, Joffret ML, Rabemanantsoa S, Andriamamonjy S, Heraud JM, Delpeyroux F - Emerging Infect. Dis. (2013)

Phylogenetic trees showing genetic relationships between sequences of vaccine-derived poliovirus (VDPV) isolates. The trees are based on nucleotide sequence alignments of various subgenomic regions. Multiple sequence alignments were performed with CLC Main Workbench 5.7.2 software (CLC bio, Aarhus, Denmark). Phylograms were constructed with MEGA 4 (http://megasoftware.net/mega4/mega.html), using the Jukes-Cantor algorithm for genetic distance determination and the neighbor-joining method. The robustness of the resulting trees was assessed with 1,000 bootstrap replications. A) Tree built from 712-bp fragments of the 5′–untranslated region (nt 36–747, with reference to Sabin 2 nucleotide numbering). B) Tree built from 2,637-bp fragments of the P1 region (nt 748–3,384). C) Tree built from 1,725-bp fragments of the P2 region (nt 3,385–5,109). D) Tree built from 2,259-bp fragments of the P3 region (nt 5,110–7,368). Names (isolate name-accession no.) are VDPV isolates recovered in Madagascar in 2011, 2005, and 2001–2002. Sequences of other isolates (CV-A11, 13, and 17) from Madagascar were also used. The percentage of bootstrap replicates is indicated at nodes if >70%. The length of branches is proportional to the number of nucleotide differences (percent divergence).Scale bars indicate genetic distances.
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Related In: Results  -  Collection

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Figure 1: Phylogenetic trees showing genetic relationships between sequences of vaccine-derived poliovirus (VDPV) isolates. The trees are based on nucleotide sequence alignments of various subgenomic regions. Multiple sequence alignments were performed with CLC Main Workbench 5.7.2 software (CLC bio, Aarhus, Denmark). Phylograms were constructed with MEGA 4 (http://megasoftware.net/mega4/mega.html), using the Jukes-Cantor algorithm for genetic distance determination and the neighbor-joining method. The robustness of the resulting trees was assessed with 1,000 bootstrap replications. A) Tree built from 712-bp fragments of the 5′–untranslated region (nt 36–747, with reference to Sabin 2 nucleotide numbering). B) Tree built from 2,637-bp fragments of the P1 region (nt 748–3,384). C) Tree built from 1,725-bp fragments of the P2 region (nt 3,385–5,109). D) Tree built from 2,259-bp fragments of the P3 region (nt 5,110–7,368). Names (isolate name-accession no.) are VDPV isolates recovered in Madagascar in 2011, 2005, and 2001–2002. Sequences of other isolates (CV-A11, 13, and 17) from Madagascar were also used. The percentage of bootstrap replicates is indicated at nodes if >70%. The length of branches is proportional to the number of nucleotide differences (percent divergence).Scale bars indicate genetic distances.
Mentions: Isolate MAD-2675–11 was shown to be a mutated Sabin 2 PV, but isolates MAD-2593–11 and MAD-2642–11 displayed mosaic recombinant genomes composed of sequences derived from Sabin 2 and other human EV-Cs. Both recombinants had the 5′–untranslated region (UTR), the nonstructural P2–P3 regions, and the 3′-UTR derived from non-PV human EV-C. The 2 recombination sites were similarly located in each of these recombinant genomes (approximately at nt 760 and nt 3,368) at the 2 extremities of the structural genomic P1 region. Although these recombinants appeared to be related, they had different non-PV human EV-C sequences in the P2–P3 region and the 3′-UTR (6.0%–20.0% nt sequence difference). The phylogenetic relationship of these isolates to the previous Madagascar VDPV2s was assessed: the 2011 isolates originated from 2 novel, independent events (Figure). The 2011 VDPVs had lost the major attenuating determinants in the 5′-UTR (guanine to adenine at nt 481) and VP1 region (isoleucine to threonine at codon 143) regions (8). This finding strongly suggests that the 2011 VDPVs had regained a degree of neurovirulence.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Poliomyelitis outbreaks caused by pathogenic vaccine-derived polioviruses (VDPVs) are primarily a result of low polio vaccine coverage... 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... Sample extracts were used to inoculate human RD and HEp-2c cells and mouse L cells expressing the human poliovirus cellular receptor CD155 (L20B cells)... Of the 616 samples, 238 induced cytopathogenic effects in human cells, of which 20 also induced cytopathogenic effects in L20B cells; the latter samples were confirmed by reverse transcription PCR molecular testing to contain PV strains... All PV isolates originated from children who had not received OPV in the 30 days before samples were collected... We sequenced the genomic regions encoding the capsid viral protein (VP1) of the 20 isolates confirmed to contain PV strains: 3 type 2 PV isolates showed >0.5% nt sequence divergence from the type 2 OPV strain (Sabin 2) and were thus identified as potentially pathogenic VDPV2s... Almost complete genomic sequencing, from nt 36 to nt 7,420 (Sabin 2 numbering), was subsequently performed (EMBL accession nos... HF913426– HF913428)... No polio cases have been reported in the province since then, suggesting that VDPV circulation was limited or stopped by these campaigns... Massive OPV immunization campaigns worldwide have greatly decreased the frequency of poliomyelitis caused by wild-type PVs... However, after the disease has been eliminated in developing countries, low polio vaccine coverage frequently enables the emergence of VDPVs or the reintroduction of wild-type PV from disease-endemic countries; both scenarios threaten the success of the poliomyelitis eradication program... More than 640 polio cases caused by circulating VDPVs have been reported in 21 developing countries... We have shown that even in the absence of polio cases, potentially pathogenic circulating VDPVs can be detected in fecal samples collected from children living in areas with fluctuating and often low polio vaccine coverage... In Madagascar, vaccination appears to have cleared emerging VDPVs and to have prevented polio cases in children.

Show MeSH
Related in: MedlinePlus