Poliovirus Type Research Articles

Public Health Response to Restore Polio Free Status in Malaysia

Malaysia started the polio immunization programme since 1972 and achieved polio-free
 certification in 2000. After 27 years from the last reported polio case in 1992, on 8 December
 2019, the Ministry of Health Malaysia announced the return of polio into the country when
 the first polio case detected in Sabah involving a 3-month-old male child (Abdullah, N.H.,
 2019). The child confirmed to be infected with vaccine-derived poliovirus type 1 (VDPV1)
 which later classified as a circulating vaccine-derived poliovirus type 1 (cVDPV1). Further
 test confirmed that the virus is genetically linked to poliovirus (PHL-NCR-2) circulating in
 the southern Philippines (Alleman, M.M. et al., 2020). To date, a total of four polio cases
 were confirmed in Sabah of which due to vaccine-derived poliovirus type 1 (VDPV1). The
 vaccine-derived poliovirus type 2 (VDPV2) was also detected from environmental samples
 taken from various locations in Sabah.

Immunogenicity and safety of a hexavalent pediatric vaccine in HIV-exposed infected and uninfected infants in Republic of South Africa

ABSTRACT Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in this population to evaluate the primary series, antibody persistence, and booster response to a licensed fully liquid hexavalent vaccine containing diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (HB), and Haemophilus influenzae type b antigens (PRP~T). This was a Phase III, open-label, randomized study conducted at a single center in the Republic of South Africa. The DTaP-IPV-HB-PRP~T vaccine was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15–18 months of age. Immunogenicity of each antigen was measured using validated assays and vaccine reactogenicity was recorded using diary cards. The low number of HIV-exposed infected participants, due to widespread pre- and peri-natal retroviral treatment, meant that between-group comparisons should be treated with caution. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HBs ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster. There were no safety concerns. In conclusion, primary series and booster vaccination of the DTaP-IPV-HB-PRP~T vaccine were immunogenic and safe in HIV-exposed infected and uninfected infants. These results were comparable to historical data in healthy infants and toddlers.

Microbiological Research of the Effects of EVODROP Silver Nanoparticle on Escherichia coli, Enterococci and Coliforms

The aim of the study was to analyze the microbiological effects of EVODROP Silver Nanoparticle. A comparative analysеs of the number of bacteria of a given species before and after influence wеre performed.
 Nanoparticle Silver makes physical changes in the bacterial membrane, like the membrane damage, which can lead to cellular contents leakage and bacterial death [1,2,3]. There are effects of Nanoparticle Silver against SARS-CoV-2. The coronavirus gets replicated via copying of the genetic material using the enzyme RNA-dependent RNA polymerase [4,5].
 The membranes of the cells of mammals don’t have peptidoglycans and Ag+ has not inhibiting effect [6]. In such a way it prevents the further alteration of the enzymes.
 In Japanese study there are proofs that Nanoparticle Silver inhibiting extracellular SARS-CoV-2 at concentrations ranging between 1 and 10 ppm while cytotoxic effect was observed at concentrations of 20 ppm and above [7]. There is objective research of the effects of Nanoparticle Silver on the virus SARS-CoV-2 with Inhalation in Israel [8].
 The author of the device EVOhygiene Fabio Huether performs liquid with concentration 20 ppm nano silver and size of nano particles 5 nm.
 The virucidal activity of silver nanoparticles (AgNPs) allows its wider application in the annihilation or amelioration of several viral infections such as Poliovirus type-1, Coxsackievirus B3, influenza A virus, SARS-CoV-2 etc. [9]
 There is publication in Nature Nanotechnology for the effects of Silver Nanoparticles as disinfectant against SARS-CoV-2 [10].
 The research show effects of EVODROP Silver Nanoparticle on the following bacteria Escherichia coli, Enterococci and Coliforms.

Randomized Controlled Clinical Trial of Bivalent Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine in Nigerian Children.

BackgroundWe conducted a trial in Nigeria to assess the immunogenicity of the new bivalent oral poliovirus vaccine + inactivated poliovirus vaccine (bOPV+IPV) immunization schedule and gains in type 2 immunity with addition of second dose of IPV. The trial was conducted in August 2016–March 2017, well past the trivalent OPV-bOPV switch in April 2016.MethodsThis was an open-label, 2-arm, noninferiority, multicenter, randomized, controlled trial. We enrolled 572 infants aged ≤14 days and randomized them into 2 arms. Arm A received bOPV at birth, 6, and 10 weeks, bOPV+IPV at week 14, and IPV at week 18. Arm B received IPV each at 6, 10, and 14 weeks and bOPV at 18 weeks of age.ResultsSeroconversion rates for poliovirus types 1 and 3, respectively, were 98.9% (95% confidence interval [CI], 96.7–99.8) and 98.1% (95% CI, 88.2–94.8) in Arm A and 89.6% (95% CI, 85.4–93.0) and 98.5% (95% CI, 96.3–99.6) in Arm B. Type 2 seroconversion with 1 dose IPV in Arm A was 72.0% (95% CI, 66.2–77.3), which increased significantly with addition of second dose to 95.9% (95% CI, 92.8–97.9).ConclusionsThis first trial on the new Expanded Program on Immunization (EPI) schedule in a sub-Saharan African country demonstrated excellent immunogenicity against poliovirus types 1 and 3 and substantial/enhanced immunogenicity against poliovirus type 2 after 1 to 2 doses of IPV, respectively.

Progress Toward Poliomyelitis Eradication - Pakistan, January 2019-September 2020.

Pakistan and Afghanistan are the only countries where wild poliovirus type 1 (WPV1) is endemic (1,2). In 2019, Pakistan reported 147 WPV1 cases, approximately 12 times the number reported in 2018. As of September 15, 72 cases had been reported in 2020. Since 2019, WPV1 transmission has also spread from Pakistan's core poliovirus reservoirs (Karachi, Peshawar, and Quetta block) to southern districts of Khyber Pakhtunkhwa (KP), Punjab, and Sindh provinces. Further, an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2), first detected in July 2019, has caused 22 paralytic cases in 2019 and 59 as of September 15, 2020, throughout the country. The coronavirus disease 2019 (COVID-19) pandemic has substantially reduced delivery of polio vaccines through essential immunization (formerly routine immunization) and prevented implementation of polio supplementary immunization activities (SIAs)* during March-July 2020. This report describes Pakistan's progress in polio eradication during January 2019-September 2020 and updates previous reports (1,3,4). The Pakistan polio program has reinitiated SIAs and will need large, intensive, high-quality campaigns with strategic use of available oral poliovirus vaccines (OPVs)† to control the surge and widespread transmission of WPV1 and cVDPV2.

Safety and immunogenicity of a new Sabin inactivated poliovirus vaccine candidate produced on the PER.C6® cell-line: a phase 1 randomized controlled trial in adults

ABSTRACT This first-in-human study (NCT03032588), conducted in Belgium, evaluated a new inactivated poliovirus vaccines (IPV) candidate based on Sabin poliovirus strains grown on the high-yield PER.C6® cell line. Healthy adults (N = 32) were randomized (1:1) to receive a single dose of PER.C6-based Sabin-IPV (sIPV, 15:35:112.5 DU/dose) or conventional Salk-IPV (cIPV, 40:8:32 DU/dose). Reactogenicity was assessed up to 7 days after vaccination, immunogenicity 28 days after vaccination, and safety up to 6 months after vaccination. Solicited adverse events (AEs) were mild to moderate, no changes of concern in vital signs or safety laboratory values were observed, and no severe AEs (SAEs) or vaccine-related unsolicited AEs were reported after vaccination. A trend to more frequent solicited AEs after sIPV than after cIPV administration was observed. Most participants had preexisting neutralizing antibodies against poliovirus types (titer ≥8), which were strongly boosted by sIPV. Post-vaccination geometric mean titers were high (≥12,000) and similar across the two vaccination groups. Only participants with very high preexisting antibody levels did not show a vaccine-induced response, defined in seropositive participants as a 4-fold titer increase. The 10 initially seronegative (titer <8) participants (n = 5 in each study group) seroconverted and all participants had seroprotective antibody levels post-vaccination. The antibodies elicited by sIPV neutralized both Sabin and Salk poliovirus strains. In conclusion, the PER.C6®-based sIPV was well tolerated and highly immunogenic in adults with preexisting antibodies to poliovirus.

Poliomyelitis seroprevalence in high risk populations of India before the trivalent-bivalent oral poliovirus vaccine switch in 2016

IntroductionThis study assessed the seroprevalence against all three polioviruses among the last cohort of infants aged 6-11 months who received tOPV before the tOPV-bOPV switch and had an opportunity to receive a full dose of inactivated poliovirus vaccine introduced in the routine immunization schedule. MethodsSerum was tested for neutralizing antibodies against polioviruses among infants residing in three different risk- category states for poliovirus transmission in India viz., Bihar historically high-risk state for polio, Madhya Pradesh a State with low routine immunization coverage and Chhattisgarh with lower acute flaccid paralysis surveillance indicators. ResultsA total of 1113 serum samples were tested across the three states. The overall seroprevalence was 98.5% (97.7-99.2), 98.9% (98.3-99.5) and 94.4% (93.0-95.8) for poliovirus types 1, 2 and 3 respectively. The median antibody titers for corresponding serotypes were 575, 362 and 181. Infants who received five doses of tOPV showed respective seroprevalence rates of 98.7%, 98.7% and 93.7% against types 1, 2 and 3 polioviruses. There was no significant difference in seroprevalence across the group of IPV recipients. The median reciprocal titers across the groups of IPV recipient was significantly higher (p = 0.006) for poliovirus-3. ConclusionThe seroprevalence rates observed in the study are historically the highest in the series of serosurveys that India has conducted to assess the population immunity against polioviruses. Poliovirus 2 seroprevalence was very high at the time of the tOPV-bOPV switch in India effected in April 2016.

Prevalence and Bayesian Phylogenetics of Enteroviruses Derived From Environmental Surveillance Around Polio Vaccine Switch Period in Shandong Province, China.

We present the results of environmental surveillance for poliovirus (PV) and non-poliovirus (NPEV) around the switch from trivalent to bivalent oral polio-vaccine (OPV) which occurred in China in May 2016. Sewage samples were collected in Jinan and Linyi city from 2015 to 2017. Enterovirus (EV) isolation, VP1 amplification, Sanger sequencing, and phylogenetic analyses were performed. Among105 sewage samples (36 in Jinan and 69 in Linyi), 101 were positive for EV, with 74.3% (78/105) PV-positive samples and 90.5% (95/105) NPEV-positive samples. A total of 893EV isolates were obtained, including 326 (36.5%) PVs and 567 (63.5%) NPEVs. Echovirus (E) -11 was the most common serotype out of 18 detected NPEV types (120/567), followed by E-3 (75/567) and E-6 (74/567). PV2 vanished and PV3 came to be the ascendant PV type in sewage after May 2016. Eight PV isolates were judged as pre-vaccine-derived poliovirus(pre-VDPV) and no VDPV or wild PV isolates were monitored. Bayesian phylogenetics demonstrated global E-11 originated in 1876 and evolved with the estimated rate of 4.63 × 10-3 nucleotide substitutions per site per year (s/s/y). Multiple circulating clusters that originated at different times were coexisting in Shandong province. The most recently common ancestor of global coxsackievirus B5 could date back to 1867, at the evolutionary rate of 3.95 × 10-3s/s/y. In conclusion, our study described the changes of PVs and NPEVs around the polio vaccine switch period and provided meaningful global molecular epidemiological data for further studies of EV-related diseases among the population.

Towards a Polio free World – the End Game Plan

Poliomyelitis, the dreaded cause of lameness, was ravaging the world in 1988; when more than 125 countries were endemic with the disease and about 350,000 new cases were reported every year. It could have been fanciful to consider eradicating the disease in any future. It was a resolve bold enough at the 41st World Health Assembly then to do it. The disease did provide epidemiological opportunities to make it a possible candidate for eradication and the idea was first realized soon in 1997; when the American region was certified as polio free; the last case being reported from Peru in 1994 (Louis Fermin Tenorio). Other regions did not fall short much; Mum Chanty of Cambodia was the last case from Western Pacific region in 1997 and the region was certified as polio free subsequently in the year 2000. Europe was the third region in the list; Melik Minas from Turkey had the disease in 1999; and the region got the same certificate in 2002.Meanwhile the story in India and South East Asian region was more protracted. Of the three types of polio viruses, the weakest one, wild type 2 was reported last from Aligarh in India in 1999. But it took another thirteen years to put a stop to the next type, wild type 3 (Pakistan in 2012). The last wild polio virus case of India and South East Asia region (onset on January 13) was found at Howrah in 2011 when poor Ruksar Khatun had contacted the disease. In 2012 India was declared no longer a polio endemic country. Later on the South East Asian region was certified as polio free on March 27, 2014. But in Africa and two countries of Eastern Mediterranean region ( Pakistan and Afghanistan ) transmission of wild polio virus continued. On July 24, 2014 last wild polio virus of Africa was detected in Nigeria. Subsequently the country interrupted wild polio virus transmission and was declared non endemic in 2015 leaving only two countries from the 125 when the journey had started. The latest of such glorious milestones was achieved when WHO certified that type 2 wild polio virus has been eradicated on September 20, 2015. The success story in India has been lauded greatly by the international community as technically speaking; the scenario had been most challenging in this country. But elsewhere, like in Afghanistan and Nigeria, things still pose problem – a huge number of children are still unreachable and the health workers being targeted with physical assaults even in 2012 and 2013.

Safety and immunogenicity of inactivated poliovirus vaccine schedules for the post-eradication era: a randomised open-label, multicentre, phase 3, non-inferiority trial

SummaryBackgroundFollowing the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule.MethodsThis randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at −10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference.. Safety was assessed as serious adverse events and important medical events. This study is registered on ClinicalTrials.gov, NCT03239496.FindingsFrom Oct 23, 2017, to Nov 13, 2018, we enrolled 773 infants (372 [48%] girls) in Panama and the Dominican Republic (two f-IPV group n=217, three f-IPV group n=178, two IPV group n=178, and three IPV group n=200). 686 infants received all scheduled vaccine doses and were included in the per-protocol analysis. We observed non-inferiority for poliovirus type 1 seroconversion rate at 40 weeks for the two f-IPV dose schedule (95·9% [95% CI 92·0–98·2]) versus the two IPV dose schedule (98·7% [95·4–99·8]), and for the three f-IPV dose schedule (98·8% [95·6–99·8]) versus the three IPV dose schedule (100% [97·9–100]). Similarly, poliovirus type 2 seroconversion rate at 40 weeks for the two f-IPV dose schedule (97·9% [94·8–99·4]) versus the two IPV dose schedule (99·4% [96·4–100]), and for the three f-IPV dose schedule (100% [97·7–100]) versus the three IPV dose schedule (100% [97·9–100]) were non-inferior. Seroconversion rate for the two f-IPV regimen was statistically superior 4 weeks after the last vaccine dose in the 14 and 36 week schedule (95·9% [92·0–98·2]) compared with the 10 and 14 week schedule (83·2% [76·5–88·6]; p=0·0062) for poliovirus type 1. Statistical superiority of the 14 and 36 week schedule was also found for poliovirus type 2 (14 and 36 week schedule 97·9% [94·8–99·4] vs 10 and 14 week schedule 83·9% [77·2–89·2]; p=0·0062), and poliovirus type 3 (14 and 36 week schedule 84·5% [78·7–89·3] vs 10 and 14 week schedule 73·3% [65·8–79·9]; p=0·0062). For IPV, a two dose regimen administered at 14 and 36 weeks (99·4% [96·4–100]) was superior a 10 and 14 week schedule (88·9% [83·4–93·1]; p<0·0001) for poliovirus type 2, but not for type 1 (14 and 36 week schedule 98·7% [95·4–99·8] vs 10 and 14 week schedule 95·6% [91·4–98·1]), or type 3 (14 and 36 week schedule 97·4% [93·5–99·3] vs 10 and 14 week schedule 93·9% [89·3–96·9]). There were no related serious adverse events or important medical events reported in any group showing safety was unaffected by administration route or schedule.InterpretationOur observations suggest that adequate immunity against poliovirus type 1 and type 2 is provided by two doses of either IPV or f-IPV at 14 and 36 weeks of age, and broad immunity is provided with three doses of f-IPV, enabling substantial savings in cost and supply. These novel clinical data will inform global polio immunisation policy for the post-eradication era.FundingBill & Melinda Gates Foundation.

In-vitro Evaluation of Antiviral Activity of Moringa oleifera Extracts against Polio virus

Background: Moringa oleifera plant parts extract have been utilized tremendously in traditional medicine, having various pharmaceutical activities such as antifungal, antibacterial and antiviral properties.&#x0D; Aim: This study was carried out to evaluate antiviral activity of aqueous extract of Moringa leaves, seeds and flowers against Polio virus isolates (Vaccine Strains P1&amp;P3), MDG-17-04852; MDG-17-04881.&#x0D; Study Design: This is a baseline study carried out to determine the efficacy of Moringa oleifera in the treatment of poliomyelitis.&#x0D; Place and Duration of Study: This study was carried out at the University of Maiduguri Teaching Hospital Maiduguri and Abubakar Tafawa Balewa University, Bauchi from September 2018 to October, 2019.&#x0D; Methods: Phytochemical substances was extracted and screened from the Moringa using standard laboratory techniques. Continuous cell line L20B cells was used to isolate polio virus. Polio virus stock was prepared and titration was carried out to determine TCID50 by Kerber’s formula, L-d(S - 0.5). Cytotoxicity of the extracts was evaluated using the end-point cytopathic effect assay. Antiviral assay and Polio virus Intratypic Differentiation (ITD) was performed using Real-Time PCR.&#x0D; Results: The results revealed present of Tannins in leaves and flowers, Alkaloids and Saponins in all the extracts, Glycosides and Steroids in leaves and Flavonoids in flowers only. Cytotoxicity of the extracts shows 50% effects in 100mg and 50mg concentrations, while 33.3% and 16.7% was observed in 25mg and 12.5mg (P&gt;.05). The titration of the tissue culture infective dose 50% (TCID50) shows that Polio virus type 1and 3 had a titre value of 106.5 and 106.25 respectively. The ITD results observed presence of Sl1 and Sl3 from the extracts.&#x0D; Conclusion: This study found that the Moringa extracts did not neutralized the Polio virus strains studied, as the phytochemicals show no antiviral activity. Therefore further study is needed in this area to ascertain its antiviral potentials against poliomyelitis.

Progress Toward Poliomyelitis Eradication - Afghanistan, January 2019-July 2020.

Wild poliovirus type 1 (WPV1) transmission is ongoing only in Afghanistan and Pakistan (1). Following a decline in case numbers during 2013-2016, the number of cases in Afghanistan has increased each year during 2017-2020. This report describes polio eradication activities and progress toward polio eradication in Afghanistan during January 2019-July 2020 and updates previous reports (2,3). Since April 2018, insurgent groups have imposed bans on house-to-house vaccination. In September 2019, vaccination campaigns in areas under insurgency control were restarted only at health facilities. In addition, during March-June 2020, all campaigns were paused because of the coronavirus disease 2019 (COVID-19) pandemic. The number of WPV1 cases reported in Afghanistan increased from 21 in 2018 to 29 in 2019. During January-July 2020, 41 WPV1 cases were reported as of August 29, 2020 (compared with 15 during January-July 2019); in addition, 69 cases of circulating vaccine-derived poliovirus type 2 (cVDPV2), and one case of ambiguous vaccine-derived poliovirus type 2 (aVDPV2) (isolates with no evidence of person-to-person transmission or from persons with no known immunodeficiency) were detected. Dialogue with insurgency leaders through nongovernmental and international organizations is ongoing in an effort to recommence house-to-house campaigns, which are essential to stopping WPV1 transmission in Afghanistan. To increase community demand for polio vaccination, additional community health needs should be addressed, and polio vaccination should be integrated with humanitarian services.

Progress Toward Poliovirus Containment Implementation - Worldwide, 2019-2020.

Since 1988, when World Health Organization (WHO) Member States and partners launched the Global Polio Eradication Initiative, the number of wild poliovirus (WPV) cases has declined from 350,000 in 125 countries to 176 in only two countries in 2019 (1). The Global Commission for the Certification of Poliomyelitis Eradication (GCC) declared two of the three WPV types, type 2 (WPV2) and type 3 (WPV3), eradicated globally in 2015 and 2019, respectively (1). Wild poliovirus type 1 (WPV1) remains endemic in Afghanistan and Pakistan (1). Containment under strict biorisk management measures is vital to prevent reintroduction of eradicated polioviruses into communities from poliovirus facilities. In 2015, Member States committed to contain type 2 polioviruses (PV2) in poliovirus-essential facilities (PEFs) certified in accordance with a global standard (2). Member states agreed to report national PV2 inventories annually, destroy unneeded PV2 materials, and, if retaining PV2 materials, establish national authorities for containment (NACs) and a PEF auditing process. Since declaration of WPV3 eradication in October 2019, these activities are also required with WPV3 materials. Despite challenges faced during 2019-2020, including the coronavirus disease 2019 (COVID-19) pandemic, the global poliovirus containment program continues to work toward important milestones. To maintain progress, all WHO Member States are urged to adhere to the agreed containment resolutions, including officially establishing legally empowered NACs and submission of PEF Certificates of Participation.

EIF4G-driven translation initiation of downstream ORFs in mammalian cells.

Comprehensive genome-wide analysis has revealed the presence of translational elements in the 3′ untranslated regions (UTRs) of human transcripts. However, the mechanisms by which translation is initiated in 3′ UTRs and the physiological function of their products remain unclear. This study showed that eIF4G drives the translation of various downstream open reading frames (dORFs) in 3′ UTRs. The 3′ UTR of GCH1, which encodes GTP cyclohydrolase 1, contains an internal ribosome entry site (IRES) that initiates the translation of dORFs. An in vitro reconstituted translation system showed that the IRES in the 3′ UTR of GCH1 required eIF4G and conventional translation initiation factors, except eIF4E, for AUG-initiated translation of dORFs. The 3′ UTR of GCH1-mediated translation was resistant to the mTOR inhibitor Torin 1, which inhibits cap-dependent initiation by increasing eIF4E-unbound eIF4G. eIF4G was also required for the activity of various elements, including polyU and poliovirus type 2, a short element thought to recruit ribosomes by base-pairing with 18S rRNA. These findings indicate that eIF4G mediates translation initiation of various ORFs in mammalian cells, suggesting that the 3′ UTRs of mRNAs may encode various products.

Case of Poliomyelitis Caused by Significantly Diverged Derivative of the Poliovirus Type 3 Vaccine Sabin Strain Circulating in the Orphanage.

Significantly divergent polioviruses (VDPV) derived from the oral poliovirus vaccine (OPV) from Sabin strains, like wild polioviruses, are capable of prolonged transmission and neuropathology. This is mainly shown for VDPV type 2. Here we describe a molecular-epidemiological investigation of a case of VDPV type 3 circulation leading to paralytic poliomyelitis in a child in an orphanage, where OPV has not been used. Samples of feces and blood serum from the patient and 52 contacts from the same orphanage were collected twice and investigated. The complete genome sequencing was performed for five polioviruses isolated from the patient and three contact children. The level of divergence of the genomes of the isolates corresponded to approximately 9–10 months of evolution. The presence of 61 common substitutions in all isolates indicated a common intermediate progenitor. The possibility of VDPV3 transmission from the excretor to susceptible recipients (unvaccinated against polio or vaccinated with inactivated poliovirus vaccine, IPV) with subsequent circulation in a closed children’s group was demonstrated. The study of the blood sera of orphanage residents at least twice vaccinated with IPV revealed the absence of neutralizing antibodies against at least two poliovirus serotypes in almost 20% of children. Therefore, a complete rejection of OPV vaccination can lead to a critical decrease in collective immunity level. The development of new poliovirus vaccines that create mucosal immunity for the adequate replacement of OPV from Sabin strains is necessary.

An epidemiological analysis of Acute Flaccid Paralysis (AFP)\xa0surveillance in Kenya, 2016 to 2018

BackgroundThe poliovirus has been targeted for eradication since 1988. Kenya reported its last case of indigenous Wild Poliovirus (WPV) in 1984 but suffered from an outbreak of circulating Vaccine-derived Poliovirus type 2 (cVDPV2) in 2018. We aimed to describe Kenya’s polio surveillance performance 2016–2018 using WHO recommended polio surveillance standards.MethodsRetrospective secondary data analysis was conducted using Kenyan AFP surveillance case-based database from 2016 to 2018. Analyses were carried out using Epi-Info statistical software (version 7) and mapping was done using Quantum Geographic Information System (GIS) (version 3.4.1).ResultsKenya reported 1706 cases of AFP from 2016 to 2018. None of the cases were confirmed as poliomyelitis. However, 23 (1.35%) were classified as polio compatible. Children under 5 years accounted for 1085 (63.6%) cases, 937 (55.0%) cases were boys, and 1503 (88.1%) cases had received three or more doses of Oral Polio Vaccine (OPV). AFP detection rate substantially increased over the years; however, the prolonged health workers strike in 2017 negatively affected key surveillance activities. The mean Non-Polio (NP-AFP) rate during the study period was 2.87/ 100,000 children under 15 years, and two adequate specimens were collected for 1512 (88.6%) AFP cases. Cumulatively, 31 (66.0%) counties surpassed target for both WHO recommended AFP quality indicators.ConclusionsThe performance of Kenya’s AFP surveillance system surpassed the minimum WHO recommended targets for both non-polio AFP rate and stool adequacy during the period studied. In order to strengthen the country’s polio free status, health worker’s awareness on AFP surveillance and active case search should be strengthened in least performing counties to improve case detection. Similar analyses should be done at the sub-county level to uncover underperformance that might have been hidden by county level analysis.

Final frontiers of the polio eradication endgame.

Focusing on the key developments since January 2019, this review aims to inform policymakers and clinical practitioners on the latest on evolving global polio epidemiology and scientific advancements to guide strategies for eradication. An upsurge in wild poliovirus type 1 cases in Pakistan and Afghanistan and an expansion of type 2 circulating vaccine-derived poliovirus transmission in multiple countries threaten the remarkable progress made over past several decades by the global eradication program. These challenges have also spurred innovation on multiple fronts, including earlier detection, enhanced environmental surveillance and safer and more affordable vaccine options. A concerted effort to adapt program strategies to address context-specific challenges and continued focus on innovations to enhance detection and response capabilities will be the key to achieve and sustain eradication of all types of polioviruses.

One-Year Decline of Poliovirus Antibodies Following Fractional-Dose Inactivated Poliovirus Vaccine.

Fractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV. A community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months. Seroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B. There was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing. NCT03286803.

Validation of the bag-mediated filtration system for environmental surveillance of poliovirus in Nairobi, Kenya.

AimsThis study compared the bag‐mediated filtration system (BMFS) and standard WHO two‐phase separation methods for poliovirus (PV) environmental surveillance, examined factors impacting PV detection and monitored Sabin‐like (SL) PV type 2 presence with withdrawal of oral polio vaccine type 2 (OPV2) in April 2016.Methods and ResultsEnvironmental samples were collected in Nairobi, Kenya (Sept 2015–Feb 2017), concentrated via BMFS and two‐phase separation methods, then assayed using the WHO PV isolation algorithm and intratypic differentiation diagnostic screening kit. SL1, SL2 and SL3 were detected at higher rates in BMFS than two‐phase samples (P < 0·05). In BMFS samples, SL PV detection did not significantly differ with volume filtered, filtration time or filter shipment time (P > 0·05), while SL3 was detected less frequently with higher shipment temperatures (P = 0·027). SL2 was detected more frequently before OPV2 withdrawal in BMFS and two‐phase samples (P < 1 × 10−5).ConclusionsPoliovirus was detected at higher rates with the BMFS, a method that includes a secondary concentration step, than using the standard WHO two‐phase method. SL2 disappearance from the environment was commensurate with OPV2 withdrawal.Significance and Impact of the StudyThe BMFS offers comparable or improved PV detection under the conditions in this study, relative to the two‐phase method.

Immunogenicity and safety of different sequential schedules of Sabin strain-based inactivated poliovirus vaccination: A randomized, controlled, open-label, phase IV clinical trial in China

BackgroundThe immunogenicity and safety of the sequential schedule of Sabin strain-based inactivated poliovirus vaccine (sIPV) and bivalent oral poliovirus vaccine (bOPV) remains poorly understood in Chinese population. MethodsA multi-center, open-label, randomized controlled trial was performed involving 648 healthy infants aged 2 months from Inner Mongolia, Shanxi, and Hebei provinces. These participants were divided into three groups: sIPV-bOPV-bOPV, sIPV-sIPV-bOPV, and sIPV-sIPV-sIPV. Doses were administered sequentially at age 2, 3, and 4 months. Neutralisation assays were tested using sera collected at 2 months and 5 months. ResultsA total of 569 were included in the per-protocol analysis. The seroconversion rates of poliovirus type 1 and 3 were 100% in all three groups, the seroconversion rate of poliovirus type 2 was 91.53% (173/189) (95% CI: 86.62–95.08) in the sIPV-bOPV-bOPV group, 98.38% (182/185) (95% CI: 95.33–99.66) in the sIPV-sIPV-bOPV group, and 99.49% (194/195) (95% CI: 97.18–99.99) in the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus types 1 and 3, the sIPV-bOPV-bOPV and sIPV-sIPV-bOPV groups were non-inferior to the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus type 2, the sIPV-sIPV-bOPV group was non-inferior to the sIPV-sIPV-sIPV group, and the sIPV-bOPV-bOPV group was inferior to the sIPV-sIPV-sIPV group. All three groups exhibited good safety, with two serious adverse events reported, that were unrelated to vaccine. ConclusionsIn china, a new vaccination schedule that including 2 doses of IPV in the national immunization programs is essential.Trial registration ClinicalTrials.govNCT04054492.