Polio eradication surveillance in Sri Lanka,2019-2023

Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,2023.The results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and socio-demographics.Data was analyzed using descriptive statistics.Results:A total of 2141 stool samples from 1644 cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)surveillance.Both polioviruses(19/1644,1.15%)and non-polio enteroviruses(73/1644,4.44%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus isolated.Wild polioviruses or circulating VDPVs were not detected among the cases.During all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14 days of receipt,ensuring timely reporting as per global guidelines.Conclusions:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance indicators.Non-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.

Type I vaccine-derived polioviruses in China from 1995 to 2019

A nation-wide case surveillance was conducted in China since 1995 for the objective of identifying acute flaccid paralysis(AFP)in children so that potential wild polioviruses and vaccine-derived poliovirus(VDPV)could be identified on time.Two outbreaks associated with type I circulating VDPVs,eight native independent type I ambiguous VDPVs(aVDPV),and one imported aVDPV were identified during the AFP case surveillance in China from 1995 to 2019.The VP1 coding region of the Chinese type I VDPVs differed from the polio vaccine strain by 1.00%–3.75%(9–34 substitutions in 906 nucleotides).Most of the Chinese type I VDPV strains shared 4 amino acid substitutions in the neutralizing antigenic(NAg)sites:3 located at the BC loop,which formed the NAg site 1,and another at NAg site 3a.All of the Chinese type I VDPVs identified during the AFP case surveillance were young VDPVs,which indicated a limited viral replication resulted from the administration of the initiating oral polio vaccine(OPV)dose.VDPVs can emerge and spread in isolated communities with immunity gaps and the circulation ceases following a mass immunization with OPV.As such,high-quality surveillance permitted very early detection and response and it played a key role in stalling the widespread circulation of the emergent cVDPV strains in China.

Stochastic Analysis for the Dynamics of a Poliovirus Epidemic Model

Most developing countries such as Afghanistan,Pakistan,India,Bangladesh,and many more are still fighting against poliovirus.According to the World Health Organization,approximately eighteen million people have been infected with poliovirus in the last two decades.In Asia,still,some countries are suffering from the virus.The stochastic behavior of the poliovirus through the transition probabilities and non-parametric perturbation with fundamental properties are studied.Some basic properties of the deterministic model are studied,equilibria,local stability around the stead states,and reproduction number.Euler Maruyama,stochastic Euler,and stochastic Runge-Kutta study the behavior of complex stochastic differential equations.The main target of this study is to develop a nonstandard computational method that restores dynamical features like positivity,boundedness,and dynamical consistency.Unfortunately,the existing methods failed to fix the actual behavior of the disease.The comparison of the proposed approach with existing methods is investigated.

Regulations for the Manufacture and Control of Live Poliovirus Vaccine: International Experience and China’s Path

The eradication of poliomyelitis is a landmark achievement in the history of public health, providing strong protection for children’s health. The introduction of the Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine is a prerequisite and safeguard for the large-scale production and use of domestically produced live poliovirus vaccines, serving as an indispensable component of vaccine safety. This article, based on archival documents, letters, collections of essays, and oral interviews, examines the historical experience of the development of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine. It contends that the emphasis on localization and the active engagement in international cooperation are critical factors in the swift introduction of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine.

天然砂与修饰砂对病毒的吸附与去除

分别在不同pH、含有不同金属阳离子及腐殖酸的脱氯自来水与蒸馏水中,研究了砂与金属氢氧化物修饰砂吸附与去除Polivirus 1(PV1)和Bacteroides fragilis phage(B.fp)的不同效果。结果显示,天然砂吸附病毒效率随水体pH的降低而增加,但当砂表面经氢氧化铝、氢氧化铁沉积修饰后,却在中性pH具有较高的吸附率。金属阳离子可促进天然砂吸附病毒,并随其浓度和价态的增加而增加,但对修饰砂作用不明显。腐殖酸对砂及修饰砂吸附病毒的影响也不同,修饰砂吸附病毒不受腐殖酸的存在及其浓度影响,而天然砂会因腐殖酸的存在及其浓度的提高而降低吸附病毒效率。在任一实验条件下,砂与修饰砂在自来水中的吸附病毒效率高于在蒸馏水中的吸附效率,扫描电镜观察显示砂与修饰砂具有明显不同的表面结构特征,这是两者具有不同吸附效率的基础。从砂与修饰砂吸附PV1的效率高于B.fp的现象说明B.fp是一个更为合适的病毒去除指示生物。本实验结果表明了金属氢氧化物修饰砂可为传统的净水工艺提供高效的病毒去除过滤介质与途径。

Inactivation of Poliovirus by Ozone and the Impact of Ozone on the Viral Genome

Objective To investigate the mechanisms underlying ozone-induced inactivation of poliovirus type 1(PV1). Methods We used cell culture, long‐overlapping RT‐PCR, and spot hybridization assays to verify and accurately locate the sites of action of ozone that cause PV1 inactivation. We also employed recombinant viral genome RNA infection models to confirm our observations. Results Our results indicated that ozone inactivated PV1 primarily by disrupting the 5′-non‐coding region(5′‐NCR) of the PV1 genome. Further study revealed that ozone specifically damaged the 80‐124 nucleotide(nt) region in the 5′-NCR. Recombinant viral genome RNA infection models confirmed that PV1 lacking this region was non‐infectious. Conclusion In this study, we not only elucidated the mechanisms by which ozone induces PV1 inactivation but also determined that the 80‐124 nt region in the 5′‐NCR is targeted by ozone to achieve this inactivation.

Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.

Bio-Inspired Computational Methods for the Polio Virus Epidemic Model

In 2021,most of the developing countries are fighting polio,and parents are concerned with the disabling of their children.Poliovirus transmits from person to person,which can infect the spinal cord,and paralyzes the parts of the body within a matter of hours.According to the World Health Organization(WHO),18 million currently healthy people could have been paralyzed by the virus during 1988–2020.Almost all countries but Pakistan,Afghanistan,and a fewmore have been declared polio-free.The mathematical modeling of poliovirus is studied in the population by categorizing it as susceptible individuals(S),exposed individuals(E),infected individuals(I),and recovered individuals(R).In this study,we study the fundamental properties such as positivity and boundedness of the model.We also rigorously study the model’s stability and equilibria with or without poliovirus.For numerical study,we design the Euler,Runge–Kutta,and nonstandard finite difference method.However,the standard techniques are time-dependent and fail to present the results for an extended period.The nonstandard finite difference method works well to study disease dynamics for a long time without any constraints.Finally,the results of different methods are compared to prove their effectiveness.

Pediatric case with vaccine-related poliovirus infection: A case report

BACKGROUND As long as oral poliovirus vaccine(OPV)is used,the potential risk for the emergence of vaccine-related polioviruses remains.CASE SUMMARY We report a case of Sabin-like type 1 poliovirus infection in an immunocompetent 17-mo-old child after receiving four scheduled doses of OPV.Somehow,the four doses did not confer full protection,possibly because of interference created by other enteroviruses.CONCLUSION The surveillance of vaccine-related polioviruses has important implications for improving health policies and vaccination strategies.Missed cases of vaccinerelated poliovirus infection might pose a potential risk to global poliovirus eradication.Therefore,the global withdrawal of OPV and a shift to the inclusion of only inactivated poliovirus vaccine in the vaccination schedule is the main objective of the polio eradication program.

A case of adverse reactions of immune thrombocytopenic purpura caused by poliovirus vaccine

The child patient, male, 4 months and 16 days old, was vaccinated orally by Type I Type III Live Attenuated Oral Poliomyelitis Vaccine (human diploid cells) at 10:45 a.m. on June 1st of 2016 in Shaoxian Community Health Service Center of our hospital. Two hours after vaccination, the child patient showed erythema scattered on the upper of the left knee, on the right calf and on the abdomen. The forearm of the left upper limb was scattered with punctate rashes. He was admitted to Department of Pediatrics of our hospital at 12:32 on June 1st of 2016. The diagnosis was 'immune thrombocytopenic purpura'. After admission, the child patient received expert consultation and systematic treatment, consequently getting better.

Temporal and Spatial Dynamics of Vaccine-Derived Poliovirus (VDPV) in Democratic Republic of Congo from 2018 to 2023

Background: The Democratic Republic of Congo (DRC) has been facing outbreaks of VDPV since 2017. These wild poliovirus variants are responsible for poliomyelitis, which is in the process of eradication.. In the following lines, we try to show the evolution of VDPV cases across the country in order to understand their chronological dynamics and seasonal influence. Methods: We conducted a cross-sectional study of of VDPV notified in the DRC from 2018 to 2023. Maps of the spatial dynamics of VDPV cases were produced from attack rates with QGIS® (3.22.8). As for temporal dynamics, time series were decomposed and presented in the form of graphs showing the chronological evolution of VDPV cases and their seasonal trend, using R.4.0 software package. Results: A total of 1196 Cases of VDPV types 1, 2 and 3 were recorded in the biological confirmation databases of the INRB and the Expanded Program of Immunization during the study period across25 provinces. The eastern part of the country reporting the most cases. The general trend is upwards, with a peak in 2022 of 527 cases, whereas in 2021 there was a notable drop of 31 cases. Analysis of the temporal breakdown suggests a seasonal pattern, with peaks between the months of September and December, considered being rainy periods in some provinces. Conclusion: During the 6 years of our study (2018 - 2023) almost all the Health Zones were hit by VDPV epidemics. The eastern part was the most impacted. The seasonal component is well marked suggesting a rise in detection in the rainy season and during pivotal periods of climate change.

Analysis of the distribution characteristics of enterovirus types based on environmental surveillance from 2013 to 2021 in Fujian Province, China

Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 2021 at six sampling sites in three cities in Fujian Province, China, were summarized. It showed that the sewage samples contained abundant viruses, but the positive rate was affected by different sampling sites. From the 520 samples, 431 PVs, 1,713 NPEVs, and 281 human adenoviruses (HAdVs) were isolated. PV isolates had been markedly affected following the adjustment of the immunization strategy. All but one PV isolate were Sabin-like strains without wild PVs. One isolate was vaccine-derived PV type 3 with 10 variation points in theVP1 region. After May 2016, PV type 2 was no longer detected, and PV type 3 became a superior serotype. Of 1,713 NPEVs, 24 serotypes were identified, including echovirus11 (E11), E6, coxsackievirus B3 (CVB3), CVB5, E7, and E3 were the predominant serotypes (37.65%, 20.96%, 11.50%, 8.87%, 8.23%, and 7.06%, respectively). The temporal dynamic of the six common serotypes was inconsistent. E3 was frequently isolated, but the number of isolates was low, with no obvious peaks. E6, E7, and CVB3 exhibited periodic changes with a high peak every three to four years, and E11 only had one high peak lasting four years. Summer-fall peaks of the echoviruses and spring-winter peaks of CVB were observed in the monthly distribution of virus isolation. The infectious isolates of various serotypes of different species identified from the sewage samples showed that ES is an essential part of pathogen surveillance.

A comparative study on environmental surveillance of enterovirus:Using a two-phase separation method and a filtration method with a mixed cellulose ester(MCE)membrane

This study aimed to compare the sensitivity of two-phase separation and the filtration method using a mixed cellulose ester(MCE)membrane to detect enteroviruses in sewage samples.From December 2015 to July 2016,four domestic sewage samples(1 L/sample)were collected monthly from the Guangzhou Liede Sewage Treatment Plant,and each sewage sample was divided into two aliquots(500 mL).The sewage sample was concentrated using the two-phase separation and the filtration method using an MCE membrane,and the treated solutions were inoculated into cells for enterovirus isolation.Polymerase chain reaction amplification,VP1 sequencing,and enterovirus molecular typing were performed on the positive isolates.The detection rates of poliovirus(PV)and non-polio enterovirus(NPEV)obtained using the filtration method using an MCE membrane were higher than those using the two-phase separation method.McNemar's test showed that the detection rates of PV,NPEV,type 1 Sabin-like(SL1),type 2 Sabin-like(SL2),and type 3 Sabin-like(SL3)strain were not statistically significant(P>0.05).In Guangdong Province,China,the detection rates for PV and NPEV were 53.13%and 62.50%(20/32),respectively.Twenty-seven PVs were isolated,three highly variable strains of the type 1 vaccine,with seven nucleotide substitutions in the VP1 region,compared with the type 1 Sabin strains.Eighty-seven strains of NPEV were isolated and nine serotypes were identified,among which coxsackievirus B3(CVB3),echovirus 6(E6),and echovirus 11(E11)were the dominant strains.The filtration method using an MCE membrane is more sensitive than two-phase separation and can be used as a robust,sensitive,and cost-effective method to isolate enteroviruses from sewage.

Simultaneous detection of enterovirus-D68 and vaccine-related poliovirus 3 in the stool samples of a 5-month hospitalized child with acute respiratory disease:A case report

Human enterovirus(EV)infections can lead to various manifestations,with variable correlations between genotypes and symptoms.Human enterovirus D68(EV-D68)was considered to be associated with acute respiratory disease and acute flaccid myelitis.In this short report,both EV-D68 and poliovirus 3 were detected in the stool of a hospitalized 5-month child who presented with acute respiratory symptoms and who was recently vaccinated with oral polio vaccine(OPV),using a metatranscriptomic high-throughput sequencing method.The nearly full-length genome sequences with complete open reading frames of EV-D68 and poliovirus 3 were assembled.One previously-reported neurovirulence-related amino acid substitution(T860N)in the EV-D68 VP1 region was observed,but the patient showed no neurological symptoms.More attention should be paid to EV-D68,and continuous multiple syndrome-based surveillance on non-polio enterovirus is called for.

Unusual substructure conformations observed in crystal structures of a dicistrovirus RNA-dependent RNA polymerase suggest contribution of the N-terminal extension in proper folding

The Dicistroviridae is a virus family that includes many insect pathogens.These viruses contain a positive-sense RNA genome that is replicated by the virally encoded RNA-dependent RNA polymerase(RdRP)also named 3D^(pol).Compared with the Picornaviridae RdRPs such as poliovirus(PV)3D^(pol),the Dicistroviridae representative Israeli acute paralysis virus(IAPV)3D^(pol) has an additional N-terminal extension(NE)region that is about 40-residue in length.To date,both the structure and catalytic mechanism of the Dicistroviridae RdRP have remain elusive.Here we reported crystal structures of two truncated forms of IAPV 3D^(pol),namelyΔ85 andΔ40,both missing the NE region,and the 3D^(pol) protein in these structures exhibited three conformational states.The palm and thumb domains of these IAPV 3D^(pol) structures are largely consistent with those of the PV 3D^(pol) structures.However,in all structures,the RdRP fingers domain is partially disordered,while different conformations of RdRP substructures and interactions between them are also present.In particular,a large-scale conformational change occurred in the motif B-middle finger region in one protein chain of theΔ40 structure,while a previously documented alternative conformation of motif A was observed in all IAPV structures.These experimental data on one hand show intrinsic conformational variances of RdRP substructures,and on the other hand suggest possible contribution of the NE region in proper RdRP folding in IAPV.

脊髓灰质炎病毒感染赤麂细胞株的实验研究

脊髓灰质炎病毒的敏感细胞范围一直局限于灵长类动物细胞。用该病毒感染处理非灵长类的赤麂肺二倍体细胞(KIZ-7901),可诱导9.0—14.7%的细胞出现染色体畸变,除见有染色体或单体断裂外,还见有断片、双着丝粒、环、互换、易位和缺失等。也可引致姐妹染色单体交换率(SCE)的显著提高。脊髓灰质炎病毒感染赤麂细胞后,不产生特异的CPE,不明显影响细胞群体的增殖。应用病毒滴定、包涵体检查,间接免疫荧光试验和电镜检查,都可查见细胞内有病毒或其抗原物质存在。这提示脊髓灰质炎病毒在非灵长类的赤麂细胞内呈现非杀细胞性感染。

紫外线和次氯酸钠对Escherichia coli和Poliovirus的消毒作用

本研究选用大肠杆菌(Escherichia coli)和脊髓灰质炎病毒(poliovirus)分别作为典型的细菌和病毒,利用培养和定量PCR的检测技术,对比研究紫外线消毒和次氯酸钠消毒对细菌和病毒的作用特点.结果表明:脊髓灰质炎病毒比大肠杆菌更难被灭活,达到1-log所需的氯剂量分别为19.2 mg·L^(-1)·min和10.14 mg·L^(-1)·min;所需的紫外线剂量分别为6.37 m J·cm^(-2)和1.81 m J·cm^(-2).定量PCR方法检测大肠杆菌和脊髓灰质炎病毒达到1-log的核酸损伤所需的紫外线剂量和氯剂量要比培养法高出1~2数量级,紫外线消毒对脊髓灰质炎病毒的RNA损伤量明显大于对大肠杆菌的DNA损伤,病毒的单链RNA对紫外线的敏感性更强,该结果与培养法正好相反.达到1-log核酸损伤脊髓灰质炎病毒所需的紫外线剂量为135 m J·cm^(-2),大肠杆菌所需的剂量为270.3 m J·cm^(-2),核酸损伤需要更多的消毒剂量,可能由于消毒过程微生物进入活性但处于非可培养状态(VBNC),以及灭活对微生物其他分子的损伤和微生物死后核酸的持续性.

Targeting PVR(CD155)and its receptors in anti-tumor therapy

Poliovirus receptor(PVR,CD155)has recently been gaining scientific interest as a therapeutic target in the field of tumor immunology due to its prominent endogenous and immune functions.In contrast to healthy tissues,PVR is expressed at high levels in several human malignancies and seems to have protumorigenic and therapeutically attractive properties that are currently being investigated in the field of recombinant oncolytic virotherapy.More intriguingly,PVR participates in a considerable number of immunoregulatory functions through its interactions with activating and inhibitory immune cell receptors.These functions are often modified in the tumor microenvironment,contributing to tumor immunosuppression.Indeed,increasing evidence supports the rationale for developing strategies targeting these interactions,either in terms of checkpoint therapy(i.e.,targeting inhibitory receptors)or in adoptive cell therapy,which targets PVR as a tumor marker.

Theoretical assessment of the impact of environmental contamination on the dynamical transmission of polio

A mathematical model for the dynamical transmission of polio is considered,with the aim of investigating the impact of environment contamination.The model captures two infection pathways through both direct human-to-human transmission and indirect human-to-environment-to-human transmission by incorporating the environment as a transition and/or reservoir of viruses.We derive the basic reproduction number R0^env We show that the disease free equilibrium is globally asymptotically stable(GAS)if R0^env<1,while if R0^env>1,there exists a unique endemic equilibrium which is locally asymptotically stable(LAS).Similar results hold for environmental contamination free sub-model(without the incorporation of the indirect transmission).At the endemic level,we show that the number of infected individuals for the model with the environ mental-related contagion is greater than the corresponding number for the environmental contamination free sub-model.In conjunction with the inequality R0<R0^env.Qnv,where R0 is the basic reproduction number for the environmental contamination free sub-model,our finding suggests that the contaminated environment plays a detrimental role on the transmission dynamics of polio disease by increasing the endemic level and the severity of the outbreak.Therefore,it is natural to implement control strategies to reduce the severity of the disease by providing adequate hygienic living conditions,educate populations at risk to follow rigorously those basic hygienic rules in order to avoid adequate contacts with suspected contaminated objects.Further,we perform numerical simulations to support the theory.

Epidemiological survey and genetic characterization of type 3 vaccine-derived poliovirus isolated from a patient with four doses of inactivated polio vaccine in Henan Province,China

Background:Vaccine-derived poliovirus(VDPV)is a potential threat to polio eradication because they can reintroduce into the general population and cause paralytic polio outbreaks,a phenomenon that has recently emerged as a prominent public health concern at the end of global polio eradication.This study aimed to describe the epidemiology and genetic characteristics of the frst VDPV identifed from a patient with acute faccid paralysis(AFP),with four doses of inactivated polio vaccine immunization in Henan Province,China in 2017.Methods:The patient was diagnosed with type 3 VDPV.Subsequently,a series of epidemiological approaches was implemented,including a retrospective search of AFP cases,rate of vaccination assessment,study of contacts,and supplementary immunization activities.Fecal samples were collected,viral isolation was performed,and the viral isolates were characterized using full-length genomic sequencing and bioinformatic analysis.Results:Phylogenetic analysis showed that the viral isolates from the patient were diferent from other reported genetic clusters of type 3 VDPV worldwide.They were identifed as a Sabin 3/Sabin 1 recombinant VDPV with a crossover site in the P2 region.Nucleotide substitutions,including U→C(472)and C→U(2493),have been identifed,both of which are frequently observed as reversion mutations in neurovirulent type 3 poliovirus.A unique aspect of this case is that the patient had been vaccinated with four doses of inactive polio vaccine,and the serum neutralizing antibody for Sabin types 1 and 3 were 1∶16 and 1∶512,respectively.Thus,the patient was speculated to have been infected with type 3 VDPV,and the virus continued to replicate and be excreted for at least 41 d.Conclusions:The existence of this kind of virus in human population is a serious risk and poses a severe challenge in maintaining a polio-free status in China.To the best of our knowledge,this is the frst report of VDPV identifed in the Henan province of China.Our results highlight the importance of maintaining a high-level vaccination rate and highly sensitive AFP case surveillance system in intercepting VDPV transmission.