| Objective:Through population and external environmental monitoring,clarify the changes in the epidemic strains of the poliovirus(PV)in Fujian Province after the polio vaccine immunization strategy was changed in May 2016,and evaluate whether the new immunization strategy completely blocked the circulation of PV2,also can provide a certain theoretical basis for maintaining the "polio-free" status in our province and formulating relevant immunization strategies in the later stages of polio eradication.Method:On the basis of routine monitoring of acute flaccid paralysis(AFP)cases,monitoring of healthy children and environmental sewage were added.Virus isolation and identification were performed on fecal specimens collected from the population and environmental sewage specimens,Virus isolation and identification were performed on fecal specimens collected from the population and environmental sewage specimens,and virus isolates underwent whole genome amplification and sequencing.Excel 2007 was used to summarize and sort the monitoring data,and SPSS 19.0 was used to analyze the distribution characteristics of poliovirus.Use Bio Edit 7.0.9.0 and Sequencher 4.1.4 to splice and align the measured poliovirus sequences,use MEGA X＿10.2.4,Simplot 3.5.1 and other bioinformatics software to analyze the poliovirus VP1 region gene characteristics and the whole genome sequence perform analysis to calculate the nucleotide sequence differences between poliovirus and Sabin vaccine strains,and analyze the attenuation sites,antigenic site mutations and recombination.Result:1.The AFP surveillance system in Fujian Province has always maintained high sensitivity and timeliness.The reported cases are distributed before and after vaccine switch.There are differences among 9 cities,but all meet the required indicators.In the distribution of age groups,the predominant age group was under 3 years old,and the number of AFP cases between 3-14 years old increased after the vaccine switch.There was no difference in the distribution of gender composition and immunization history.In3956 AFP cases and stool samples from nearby contacts,62 strains(1.6%)were positive for PV isolation.The isolation rates before and after vaccine switch were 1.9%(38/1986)and 1.2%(24/1970),respectively.No difference was statistically significant.After the vaccine switch,a survey of the infection rate of healthy children was carried out at different stages,and PV separation replaced 2.3%(27/1161).From 2013 to 2020,the positive rate of PV in environmental sewage monitoring specimens was 43.1%(196/455),and it was 27.5%(39/142)and 50.2%(157/313)before and after vaccine switch,which was significantly higher than before switch.It is suggested that the isolation rate of poliovirus in sewage is the highest.2.A total of 516 poliovirus strains were monitored from 3 different sources,including 62 AFP cases,27 healthy children,and 427 sewage strains,all of which were identified as vaccine-associated poliovirus(VAPV).Among the 38 strains of AFP cases before vaccine switch,there were 6 strains were PV1,13 strains were PV2,and 19 strains were PV3.Except for 1 strain of PV3,which was highly variant,the number of nucleotide variations in the VP1 region of the remaining 37 strains were all less than6.There were 7 strains of PV1 and 17 strains of PV3 among 24 strains after vaccine switch,and among them were 5 strains of type 3 vaccine-derived poliovirus(VDPV),and VP1 region of the remaining 19 strains all have less than 6 nucleotide variants.27 strains are from healthy children,all of which are PV3 type,the number of nucleotide variations in the VP1 region of which are less than 5,involving 17 loci.427 strains originated from sewage were polio vaccine strains,74 strains were isolated before the vaccine switch,involving 5 PV1,49 PV2 and 56 PV3;353 strains were isolated after vaccine switch,involving 56 PV1 and 297 PV3.The nucleotide variants number in VP1 region of 61 PV1 are all less than 5.Before the switch,PV3 vaccine strain was monitored 1 high variant strain and 1 recombinant strain.After switch,1 high variant strain and 1 strain was VDPV,the remaining strains’ VP1 variations number are all less than 5,and most of the variations are less than 2.It can be seen that after the vaccine switch,the PV2 virus was no longer monitored in Fujian Province,suggesting that the PV2 vaccine strain has been eliminated.After the vaccine switch,PV3 type became the absolute dominant serotype,and the highly variant strains and VDPV found were also PV3.3.The whole genome sequence analysis of 47 representative strains showed that among the 16 representative PV1 strains,the average nucleotide sequence difference(0.47%)between the representative strains before the vaccine switch and the Sabin1 vaccine strain was greater than that after the vaccine switch(0.11%).Among the 30 representative PV3 strains,the average difference(3.43%)between the representative strains before the vaccine switch and the Sabin3 vaccine strain was no different from that after vaccine switch(4.00%).3 strains of PV1(3/16,18.6%)and 23 strains of PV3(23/30,76.7%)were recombined.Regardless of PV1 or PV3,10 strains(83.3%)of the12 recombinant strains before vaccine switch recombined with PV2 type.After the vaccine switch,all 14 recombinant strains were not found to recombine with PV2,confirming once again that PV2 has been eliminated in Fujian Province.Among the 16 representative PV1 strains,4 cases(62.5%,4/7 cases of AFP)had residual paralysis,and the isolates(5 strains)all showed 1～3 reverse mutations at attenuated sites.However,the other 3 cases without reverse mutation at the attenuation site had no residual paralysis,suggesting that the reverse mutation at the attenuation site may be closely related to the severity of the case.There are 10 cases(52.6%,10/19 cases of AFP)with residual paralysis among the representative strains of PV3,and the isolates(10 strains)all have 1 to 4 back mutations.But there is no residual paralysis in P19-120-2 cases,the strain also has one attenuation site reverse mutation,and all isolates of residual paralysis cases have more than two types of mutations(recombination,attenuation site reverse mutation,antigenic site mutation),showing that the mutation at a single attenuation site may not be enough to make it disabled,and other factors still need to work together.Conclusion:1.Before and after the vaccine switch,the separation rate of PV in the population and the environment did not change,and the vaccine switch did not affect the distribution of PV.2.PV2 was the dominant strain of PV serotype before the vaccine switch,and PV3 replaced PV2 as the dominant serotype after the vaccine switch.The monitoring data indicated that Fujian Province has blocked the circulation of the PV2 vaccine strain and achieved the elimination of PV2.3.Recombination is common in polio isolates,and the variation of key virulence sites and antigenic sites is related to the virulence of the virus.4.On the basis of routine AFP case monitoring,sewage and healthy population monitoring can further improve the sensitivity of polio monitoring.The combination of population and external environmental monitoring can fully explain the variation of poliovirus epidemics in Fujian Province,also can provide a certain theoretical basis for maintaining the "polio-free" status in our province and formulating relevant immunization strategies in the later stages of polio eradication. |
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