Poliovirus Research Articles

Development of an animal component free production process for Sabin inactivated polio vaccine

Inactivated polio vaccine production using attenuated Sabin strains (sIPV) instead of wild type polio viruses (cIPV) is an initiative encouraged by the World Health Organization. This use of attenuated viruses is preferred as it reduces risks related to potential outbreaks during IPV production. Previously, an sIPV production process was set up based on the cIPV production process. Optimizing this process while using only animal component free (ACF) substances allows reduction of operational costs and mitigates risks of adverse effects related with animal derived compounds. Here, development of a process for production of sIPV using only ACF compounds, is described.The upstream process required a change in cell growth medium from serum-containing medium to ACF medium, while virus production media remained the same as the already used M199 medium was free of animal components. In the downstream process multiple modifications in existing unit operations were made including addition of a diafiltration step prior to inactivation. After optimizing each unit operation, robustness of the whole process was demonstrated using design of experiments (DoE) methodology. By using DoE we were able to vary different process parameters across unit operations to assess the impact on our quality attributes. The developed process was robust as the observed variation for quality attributes due to differences in process parameters remained within specification.The resulting pilot process showed not only to be robust, but also to have a considerable higher product yield when compared to the serum containing sIPV process. Product yields are now comparable to the cIPV process based on using wild type polio viruses. Moreover, the potency of the produced vaccine was comparable that of cIPV vaccine. The developed ACF sIPV process can be transferred to vaccine manufacturers at the end-of pre-clinical development phase, at lab- or pilot scale, before production of clinical trial material.

Pakistan: Walking the Last Mile for Eradicating Polio – We are Stumbling

The pressure of disease eradication can be enormous. Pakistan and Afghanistan are 2 endemic countries that are expected to give the final push to Wild Polio Virus out of planet. Polio Eradication is the largest program the world has known and has the largest frontline workforce that knocks at every door in the country. Pakistan had 15 months period where no human paralytic case of wild polio virus was reported, the program was thought to be headed in the right direction when suddenly, the outbreak happened in northwest part of Pakistan with multiple paralytic cases clustered in time and space. It was only after the detection of these cases that program’s telescope turned to this part of Pakistan that had longstanding issues which were not unknown. The outbreak has now spread to other parts of Pakistan. In this article, the author narrates her experience from the field that highlight the issues with roots that penetrate deep in the systems and hamper not only the progress of Polio Eradication but also, why overall health investments do not reach masses adequately. The author also presents the solution(s) that need to be implemented by overturning “one size fits all approach”. This entails local policy making through firsthand community interaction instead of policies made in fancy offices far away from these communities.

Vaccine-associated paralytic poliomyelitis in a child: fast transformation from Sabin-like virus to vaccine-derived poliovirus triggered an epidemiological response in two countries of the European region

ObjectivesThe detection of a vaccine-derived poliovirus (VDPV) requires an epidemiological assessment and response. Using repeated stool sampling from a child who is immunocompetent and was vaccinated against poliomyelitis with acute flaccid paralysis, a case of an extremely rapid evolution of Sabin-like poliovirus (PV) type 3 was traced in the child's body. MethodsThe case was independently identified in two countries—Tajikistan and Russia. Stool samples for the study were also independently collected in two countries on different days from the onset of paralysis. Virological, serological, and molecular methods; full genome Sanger; and high-throughput sequencing were performed to characterize isolates. ResultsPV isolates from samples collected on days 2, 3, and 14 contained eight, seven, and seven mutations in the VP1-coding region, respectively, and were classified as Sabin-like PV type 3. The isolates from samples collected on days 15 and 18 had 11 mutations and were classified as vaccine-derived PVs, which required an epidemiological response in the two countries. ConclusionThe results indicate the need to continue acute flaccid paralysis surveillance, maintain high vaccination coverage, and develop and introduce new effective, genetically stable PV vaccines.

High-throughput analysis of anti-poliovirus neutralization antibody titre in human serum by the pseudovirus neutralization test

To monitor vulnerability of countries to poliovirus (PV) outbreaks, serosurveillance of anti-PV neutralization antibody is conducted by conventional PV neutralization test (cPNT), which uses live PV strains. We previously developed a pseudovirus PV neutralization test (pPNT) as an alternative to cPNT, which uses PV pseudovirus that expresses luciferase as a reporter in the infection without producing infectious PV. In the present study, we established a high-throughput pPNT (HTpPNT) for a large-scale serosurveillance. The HTpPNT system was evaluated with 600 human serum samples obtained from a broad range of age groups of healthy volunteers (ages of 0–89 years). HTpPNT showed high correlation with cPNT (R2 for anti-type 1, 2, and 3 PV neutralization antibody titres are 0.90, 0.84, and 0.90, respectively). By using HTpPNT, we analyzed relative neutralizing antibody titre of the sera against a type 1 PV wild-type strain (Mahoney strain) to that against the type 1 Sabin strain. As a result, a correlation between the age (≥ 60 years) and the relative neutralizing antibody titre was observed (n = 15–16, P = 0.0000023–0.041), while the types of PV vaccine (i.e., oral PV vaccine and Sabin strain-based IPV) had no effect. HTpPNT would serve as a useful alternative to cPNT in a large-scale serosurveillance.

Generating Anti-TIGIT and CD155 Monoclonal Antibodies for Tumor Immunotherapy

AbstractMany studies have confirmed that the human poliovirus receptor (PVR; CD155) is related to tumor cell migration, invasion, and thus tumor progression. A PVR receptor binds its ligand T cell Ig and the ITIM domain (TIGIT) to inhibit the function of T and NK cells, thereby allowing tumors to evade immune surveillance. In this study, two IgG1 monoclonal antibodies, anti-CD155 and anti-TIGIT, were expressed by the mammalian transient transfection system, then, antibody-dependent cell-mediated cytotoxicity, antibody-binding affinity, and antitumor efficacy were evaluated subsequently in vitro. In this work, protein A affinity chromatography was used for antibodies' purification. Analysis methods included Western blot, enzyme-linked immunosorbent assay, and flow cytometry. Our data suggested that both the two monoclonal antibodies have a purity of higher than 90%, and bound tightly to the antigen with dissociation constant (K d) and 50% effective concentrations (EC50) below micromolar range. Most notably, these antibodies promote antitumor activity of immune cells in vitro. Therefore, our study laid down the foundation for subsequent in vivo experiments for further evaluation.

Assessment Level of Knowledge about Supplementary Polio Immunization in Mothers Presenting to Pediatric Population

Introduction: Humans are the only known reservoir of polio virus. Polio virus infection in humans can cause a crippling paralysis in a fraction of the infected patients. Due to permanent nature of the paralysis, low mutation rate of the virus, restriction of polio virus to human hosts and overall feasibility of polio eradication, the polio virus became the target of aggressive vaccination campaigns via supplemental polio immunization (SPI) across the world for more than two decades. To determine the level of knowledge about supplementary polio immunization in mothers presenting to pediatric Population. Materials and Methods: This study was conducted in the Pediatric Department, OPD, District General hospital Timergara from 29-04-2021 to 29-7-2022. Through a descriptive, cross-sectional study design, 216 mothers of children aged 0-5 years, accompanying their children to the pediatric OPD, were included in the study through a consecutive manner and interviewed using a structured questionnaire. Results: In this study 216 mothers were included. Mean age of the mothers was 30.97 years. Most mothers had average level of knowledge (48.6%) while 30.6% had poor level of knowledge regarding supplementary polio immunization. Most common religion was Islam (96.3%). Illiteracy was the most common educational status (32.9%) followed by secondary (22.7%) and primary (19.4%) education. Majority (58.8%) of mothers were housewives. Pearson Chi Square test for Level of Knowledge wise stratification of Educational Status of the mother gave a value of 2=45.793 and was significant at p<0.05. Level of Knowledge wise stratification of Religion of the mother had 9 cells (75%) with expected count less than 5. Level of Knowledge wise stratification of Occupational status of the mother had 2=10.148 with p=0.11(i.e.>0.05). Finally, the Level of Knowledge wise stratification of Age groups of mothers had 2=2.87 with p=0.94(i.e. >0.05). Conclusion: Level of Knowledge of mothers regarding supplementary polio immunization is significantly associated with maternal educational status Keywords: Polio, supplementary polio immunization, polio drops

Long-Term Immunogenicity of Inactivated and Oral Polio Vaccines: An Italian Retrospective Cohort Study.

Oral and inactivated poliovirus (PV) vaccines have contributed toward the global eradication of wild PV2 and PV3, as well as the elimination of PV1 in most countries. While the long-term (>5–10 years) persistence of protective antibodies in ≥80% of the population vaccinated with ≥3–4 doses of oral poliovirus vaccine (OPV) has been demonstrated, the duration of immunity in people vaccinated with the inactivated poliovirus vaccine (IPV) is still unclear. This study evaluated the seroprevalence of anti-PV neutralizing antibodies and the long-term immunogenicity conferred by OPV and IPV in a sample of medical students from the University of Bari (April 2014–October 2020). The levels of neutralizing PV1, PV2, and PV3 antibodies in blood samples taken during the assessments were evaluated. Neutralizing antibodies against PV1, PV2, and PV3 were present in >90% of the study participants, with rates of >99%, >98%, and ~92–99%, respectively. IPV resulted in a higher immunological response than OPV against PV3. Protective antibodies against all three viruses persisted for at least 18 years after administration of the last vaccine dose. Until PV1 is completely eradicated, maximum vigilance from public health institutions must be maintained.

Retrograde axonal transport of poliovirus and EV71 in motor neurons

Poliovirus (PV) can spread through neural pathway to the central nervous system and replicates in motor neurons, which leads to poliomyelitis. Enterovirus 71 (EV71), which is closely related to PV, is one of the causative agents of hand-foot-and-mouth disease and can cause severe neurological diseases similar to poliomyelitis. Since PV is similar to EV71 in its motor neurotoxicity, we tried to understand if the results obtained with PV are of general applicability to EV71 and other viruses with similar characteristics. Using microfluidic devices, we demonstrated that both PV capsid and the PV genome undergo axonal retrograde transport with human PV receptor (hPVR), and the transported virus replicated in the soma of hPVR-expressing motor neurons. Similar to PV in hPVR-transgenic (Tg) mice, neural pathway ensuring spreading of EV71 has been shown in adult human scavenger receptor class B, member 2 (hSCARB2)-Tg mice. We have validated this finding in microfluidic devices by showing that EV71 is retrogradely transported together with hSCARB2 to the cell body where it replicates in an hSCARB2-dependent manner.

Understanding the reasons for refusal of polio vaccine by families in Quetta Block, Pakistan.

Global polio eradication is a goal yet to be achieved in countries like Pakistan. In recent years, the Polio Eradication Initiative has been making steady progress with good campaign coverage and low numbers of polio cases. However, in 2019 Pakistan reported 146 cases compared to 12 in 2018. A major factor cited for this regression was a surge in vaccine refusals by parents and caretakers. To assess the reasons for the refusal of polio vaccination in Quetta Block, Balochistan. The study was conducted using data acquired from 2 polio vaccination campaigns over 3 months in 2019. The data were collected in Quetta Block, a highly endemic zone having continuous transmission of the polio virus over several years. The data were analysed using the statistical software, SPSS, version 20. We used descriptive statistics to demonstrate the characteristics of the study population. Categorical variables were measured as frequencies and percentages. Refusal rates were almost 8.6% for the polio campaign of April and 8.1% for June 2019. Misconceptions about vaccines made up 56.4% of reasons for refusals, followed by religion 16%. Misconceptions about the vaccine are the main driving force behind vaccine refusals in the study setting. Efficient strategies are required to address misconceptions in this red zone of poliovirus transmission in Balochistan.

Recovery of enteroviruses and poliovirus in Harare sewage using the bag-mediated filtration system at the introduction of the inactivated polio vaccine in Zimbabwe

Environmental surveillance is a sensitive method for detecting circulating virus in the absence of clinical cases and is important for monitoring progress for poliovirus (PV) eradication. This study used the bag-mediated filtration system (BMFS) to determine PV and enterovirus (EV) prevalence in sewage at the transition from oral polio vaccine type 2 (OPV2) use to inactivated polio vaccine (IPV) use in Zimbabwe, and examined the correlation between environmental surveillance results and vaccination coverage of OPV. A total of 18 BMFS samples from 6 sampling sites were analysed for the presence of EV and PV via direct RT-qPCR, direct ITD (intratypic differentiation), and the WHO algorithm. EV prevalence in Harare wastewater was 88.9% (16/18) using direct RT-PCR, 61.1% (11/18) using direct ITD, and 77.8% (14/18) using the WHO algorithm. Of the 18 samples analysed using the WHO algorithm, 10 samples (55.6%) were positive for Sabin-like PV type 3 (SL3). Of these 10 samples, 2 were also positive for non-polio enteroviruses (NPEV), resulting in a total of 6 (33.3%) samples positive for NPEV and 4 negative. The sensitivity of isolation in detecting EVs in sewage was 92.9% when comparing direct RT-qPCR results to the WHO algorithm. Using direct ITD, two high-density, low-income sampling sites were negative for SL3 and one low-density, high-income sampling point was negative for SL3 using the WHO algorithm. There was a strong association between relative EV concentration and the number of OPV3 vaccine recipients (r = 0.8590; p = 0.0284) in sampled areas. This study demonstrated the ability of BMFS to detect PVs circulating in Harare wastewater at the beginning of the OPV–IPV switch and can be used to monitor potential reintroduction of wild PV or vaccine-derived PVs from endemic areas.

History of the Wastewater Assessment of Polio and Non-Polio Enteroviruses in the Slovak Republic in 1963-2019.

We describe the genesis of poliovirus (PV) and non-polio enterovirus (NPEV) surveillance program of sewage wastewaters from its inception to the present in the Slovak Republic (SR). Sampling procedures and evolution of the methodology used in the SR for the detection of PVs and NPEVs are presented chronologically. For statistical data processing, we divided our dataset into two periods, the first period from 1963 to 1998 (35 years), and the second period from 1999 to 2019 (21 years). Generalized additive models were used to assess temporal trends in the probability of occurrence of major EV serotypes during both periods. Canonical correspondence analysis on relative abundance data was used to test temporal changes in the composition of virus assemblages over the second period. The probability of occurrence of major viruses PV, coxsackieviruses (CVA, CVB), and Echoviruses (E)) significantly changed over time. We found that 1015 isolated PVs were of vaccine origin, called “Sabin-like” (isolates PV1, PV2, PV3). The composition of EV assemblages changed significantly during the second period. We conclude that during the whole period, CVB5, CVB4, and E3 were prominent NPEVS in the SR.

Incidence of Poliovirus Infection in Patients with Severe Combined Immunodeficiency (SCID)

Background: Severe combined immunodeficiency (SCID) is a group of disorders with impairment in function of T, B and sometimes NK cells that could lead to high susceptibility to infectious diseases and premature death. Live-attenuated vaccines are contraindicated in SCID patients. However, in regions without screening programs for SCID, oral polio vaccine (OPV) could lead to vaccine-derived polioviruses (VDPVs) which are reverted to the neurovirulent virus types and could cause outbreaks of vaccine-associated paralytic poliovirus (VAPP) in communities with inadequate vaccine coverage.
 Method: 20 SCID patients registered in Iranian national registry for Primary immunodeficiency (PID) disorders were tested for polio virus stool shedding. The demographic data, clinical presentation, polio test results, laboratory data and whole exome sequencing (WES) of the patients were available.
 Results: Among the 20 SCID patients enrolled in the study, 6 patients tested positive for immunodeficiencyrelated VDPVs (iVDPV) shedding. Four patients (20%) had iVDPV type 2, one patient (5%) had iVDPV type 1 and one patient (5%) had iVDPV type 3.
 Conclusion: Due to the high possibility of asymptomatic and long-term iVDPV shedding in SCID patients, the enhancement of screening of PID patients for poliovirus and iVDPV excretion is strongly needed.

Environmental Surveillance of Poliovirus in Four Districts within Two Regions of Ghana

The eradication of poliovirus is at its last phase through the efforts and strategies of Global Polio Eradication Initiation (GPEI). There are very few countries that are still endemic with Wild Poliovirus (WPV) and others with circulating Vaccine Derived Poliovirus (cVDPV). The aim of the study was to detect silent circulation of WPV and VDPV in four districts within the Eastern and Volta region of Ghana. A systematic longitudinal design was used for the study. The convenient sampling technique was used to collect the samples every four weeks from two open and close sewage systems. The open sewage systems were located in New Juabeng and Ho districts while the close sewage systems were located in Asuogyaman and Ketu South districts. A total of 35 sewage samples were collected from September 2018 to May 2019. L20B and RD cell lines were used for the purification of Poliovirus (PV) while real-time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) was use to characterize the serotypes of the PVs. The findings of the study showed that the prevalence of Non-Polio Enterovirus (NPEV) and Sabin were 65.71% and 14.29% respectively. The characterized Sabins were serotype 1 and serotype 3 which were circulating in the two districts within the Eastern Region. The study did not detect any WPV and VDPV but isolated Sabin strains of the poliovirus. This necessitates the need for continuous environmental surveillance for poliovirus nationwide.

Application of Silver Nanoparticles as a New Alternative Antiviral Agent for SARS-CoV-2: A Review

Background: Today, SARS-CoV-2 (COVID-19), a viral disease caused by the novel coronavirus (a tiny crowned virus), has become one of the threats for human beings all over the world and caused the death of millions of people worldwide. Many vaccines have been developed and administered to people in several countries; however, due to their propensity to create new strains, it appears that curing all corona strains will be challenging. So, it is necessary to identify the structure of the virus, mechanism of action, and its antiviral activities against drugs and other functional materials. Method: AgNPs have unique physicochemical and antimicrobial properties. This review describes the structure and nature of the virus and the mechanism of action of an antiviral drug such as silver nanoparticles (AgNPs) with the virus. In addition, different methods for synthesis of AgNPs, application of AgNPs as an antiviral agent against influenza virus, human immuno deficiency virus (HIV), herpes simplex virus type 1 (HSV-1), hepatitis B virus (HBV), polio virus, respiratory syncytial virus (RSV), are discussed. Also, the most probable applications and properties of AgNPs that can help prepare it as an antiviral agent are discussed. Results: The use of AgNPs against various viruses, including the coronavirus family, is found to be effective; therefore, it can be considered for the development of antiviral agents, disinfectants, antiviral coated mask, and their therapeutic use against the treatment of novel coronavirus with minimum side effect and great efficiency. Conclusions: AgNPs were successfully used for the treatment of various viral diseases of the coronavirus family such as H1N1, H3N2, influenza, even for SARS and MERS coronaviruses. AgNPs coated masks, disinfectants, fabrics, wipes, and inhalation systems are effective for the inhibition of SARS-CoV-2 infection. Since sanitizers have a temporary effect, the development of some other potential alternatives having low toxicity, ease of use, long lasting efficiency, health cautiousness, minimum side effect, sustainable fabrics is required.

Renegade cellular genetic sequences in stealth adapted viruses: introducing a new era of virology

DNA sequence data have previously been obtained on an African green monkey simian cytomegalovirus (SCMV)-derived stealth adapted virus. The virus was repeatedly cultured from a patient with the chronic fatigue syndrome (CFS). The data reveal not only genetic sequences that are derived from regions of the SCMV genome, but also the unexpected presence of genetic sequences that have originated from portions of the human cellular genome. The SCMV-derived stealth adapted virus has also acquired foreign genetic sequences of bacterial origin. The focus of this article is on the potential mechanism as well as the major biological and clinical ramifications of the primate to human and subsequent human to human viral transmission of genetically unstable renegade cellular genetic sequences. Insight into this topic has come from further analysis of rhesus monkey-derived cellular sequences in the stealth adapted viruses cultured from two other CFS patients and a mixture of both rhesus and human genome-derived cellular sequences in the virus cultured from another CFS patient. The virus acquired monkey cellular sequences are subject to ongoing mutations and can be replaced by human cellular sequences, probably by homologous recombination. There is a genetic basis for many human diseases, including cancers. The potential acquisition of pathogenic cellular sequences by stealth adapted viruses may, therefore, result in some of these genetic diseases becoming infectious. Stealth adapted viruses have been cultured from patients with a range of neurological and psychiatric illnesses, yet their existence is still not officially acknowledged by Public Health officials. The political reluctance to do so stems in part from the clearly implied origins of some stealth adapted viruses from the use of kidney cells from cytomegalovirus contaminated monkeys to produce live polio virus vaccines. It is imperative that the culturing and genetic analyses of stealth adapted viruses be pursued.

Contribution of Auto-Visual AFP Detection and Reporting (AVADAR) on polio surveillance in South Sudan.

Introductionthe last wild polio virus in South Sudan was documented in 2009. Nonetheless, it was one of the last four countries in the WHO African region to be accepted as a polio-free country in June 2020. In line with this, to accelerate the polio-free documentation process, the country has piloted Auto Visual AFP Detection and Reporting (AVADAR) in three counties. This study examined the contribution of the AVADAR surveillance system to the traditional Acute Flaccid Paralysis (AFP) surveillance system to document lessons learnt and best practices.Methodswe performed a retrospective descriptive quantitative study design to analyze secondary AVADAR surveillance data collected from June 2018 to December 2019 and stored at the WHO AVADAR server.Resultsthe AVADAR community surveillance system has improved the two main AFP surveillance indicators in the piloted counties and made up 86% of the total number of true AFP cases detected in these counties. The completeness and timeliness of weekly zero reporting were 97% and 94%, respectively and maintained above the standard throughout the study, while the two main surveillance indicators in the project area were improved progressively except for the Gogrial West County. In contrast, main surveillance indicators declined in some of the none-AVADAR implementing counties.Conclusionthe AVADAR surveillance system can overcome the logistical and remoteness barriers that can hinder the early detection and reporting of cases due to insecurity, topographical, and communication barrier in rural and hard-to-reach areas to accomplish and sustain the two main surveillance indicators, along with the completeness and timeliness of weekly zero reporting. We recommend extending this application-based surveillance system to other areas with limited resources and similar challenges by incorporating other diseases of public health concern.

Spatial analysis of genetic clusters and epidemiologic factors related to wild poliovirus type 1 persistence in Afghanistan and Pakistan.

Following the certification of the World Health Organization Region of Africa as free of serotype 1 wild poliovirus (WPV1) in 2020, Afghanistan and Pakistan represent the last remaining WPV1 reservoirs. As efforts continue in these countries to progress to eradication, there is an opportunity for a deeper understanding of the spatiotemporal characteristics and epidemiological risk factors associated with continual WPV1 circulation in the region. Using poliovirus surveillance data from 2017-2019, we used pairwise comparisons of VP1 nucleotide sequences to illustrate the spatiotemporal WPV1 dispersal to identify key sources and destinations of potentially infected, highly mobile populations. We then predicted the odds of WPV1 detection at the district level using a generalized linear model with structural indicators of health, security, environment, and population demographics. We identified evidence of widespread population mobility based on WPV1 dispersal within and between the countries, and evidence indicating five districts in Afghanistan (Arghandab, Batikot, Bermel, Muhamandara and Nawzad) and four districts in Pakistan (Charsada, Dera Ismail Khan, Killa Abdullah and Khyber) act as cross-border WPV1 circulation reservoirs. We found that the probability of detecting WPV1 in a district increases with each armed conflict event (OR = 1·024, +- 0·008), level of food insecurity (OR = 1·531, +-0·179), and mean degrees Celsius during the months of greatest precipitation (OR = 1·079, +- 0·019). Our results highlight the multidisciplinary complexities contributing to the continued transmission of WPV1 in Afghanistan and Pakistan. We discuss the implications of our results, stressing the value of coordination during this final chapter of the wild polio virus eradication initiative.

Polio eradication in a chronic conflict setting lessons from the Republic of South Sudan, 2010-2020.

Introductionin 1988 the World Health Assembly set an ambitious target to eradicate Wild Polio Virus (WPV) by 2000, following the successful eradication of the smallpox virus in 1980. South Sudan and the entire African region were certified WPV free on August 25, 2020. South Sudan has maintained its WPV free status since 2010, and this paper reviewed the country’s progress, outlined lessons learned, and describes the remaining challenges in polio eradication.Methodssecondary data analysis was conducted using the Ministry of Health and WHO polio surveillance datasets, routine immunisation coverage, polio campaign data, and surveys from 2010 to 2020. Relevant technical documents and reports on polio immunisation and surveillance were also reviewed. Data analysis was conducted using EPI Info 7 software.Resultsadministrative routine immunisation coverage for bivalent Oral Polio Vaccine (OPV) 3rd dose declined from 77% in 2010 to 56% in 2020. In contrast, the administrative and post-campaign evaluation coverage recorded for the nationwide supplemental polio campaigns since 2011 was consistently above 85%; however, campaigns declined in number from four in 2011 to zero in 2020. Overall, 76% of notified cases of Acute Flaccid Paralysis (AFP) received three or more doses of the oral polio vaccine. The Annualized Non-AFP rate ranged between 4.0 to 5.4 per 100,000 under 15 years populations, and stool adequacy ranged from 83% to 94%.ConclusionSouth Sudan’s polio-free status documentation was accepted by the ARCC in 2020, thereby enabling the African Region to be certified WPV free on August 25, 2020. However, there are concerns as the country continues to report low routine immunisation coverage and a reduction in the number of polio campaigns conducted each year. It is recommended that the country conduct high-quality nationwide supplemental polio campaigns yearly to achieve and maintain the required herd immunity. It invests in its routine immunisation program while ensuring optimal AFP surveillance performance indicators.

PKR Binds Enterovirus IRESs, Displaces Host Translation Factors, and Impairs Viral Translation to Enable Innate Antiviral Signaling.

ABSTRACTFor RNA virus families except Picornaviridae, viral RNA sensing includes Toll-like receptors and/or RIG-I. Picornavirus RNAs, whose 5′ termini are shielded by a genome-linked protein, are predominately recognized by MDA5. This has important ramifications for adaptive immunity, as MDA5-specific patterns of type-I interferon (IFN) release are optimal for CD4+T cell TH1 polarization and CD8+T cell priming. We are exploiting this principle for cancer immunotherapy with recombinant poliovirus (PV), PVSRIPO, the type 1 (Sabin) PV vaccine containing a rhinovirus type 2 internal ribosomal entry site (IRES). Here we show that PVSRIPO-elicited MDA5 signaling is preceded by early sensing of the IRES by the double-stranded (ds)RNA-activated protein kinase (PKR). PKR binding to IRES stem-loop domains 5–6 led to dimerization and autoactivation, displaced host translation initiation factors, and suppressed viral protein synthesis. Early PKR-mediated antiviral responses tempered incipient viral translation and the activity of cytopathogenic viral proteinases, setting up accentuated MDA5 innate inflammation in response to PVSRIPO infection.

Routine Immunization Programs for Children during the COVID-19 Pandemic in Ecuador, 2020-Hidden Effects, Predictable Consequences.

The COVID-19 pandemic has led to a global disruption of several services, including routine immunizations. This effect has been described in several countries, but there are few detailed studies in Latin America and no reports in Ecuador. Therefore, this work aims to quantify the reduction in routine immunizations for infants during the 2020 COVID-19 pandemic in Ecuador. 2018, 2019, and 2020 data were obtained from the Ministry of Health, Ecuador. The number of doses and the extent of immunization coverage was descriptively compared for four vaccines: rotavirus (ROTA), poliovirus (PV), pneumococcal (PCV), and pentavalent (PENTA) vaccines. There was no significant difference in doses applied during the 2018 and 2019 years. However, a significant (p < 0.05) drop of 137,000 delivered doses was observed in 2020 compared to the pre-pandemic years. Reductions in the percentage of coverage were more pronounced for the PENTA vaccine (17.7%), followed by PV (16.4%), ROTA (12%), and PCV vaccines (10.7%). Spatial analysis shows a severe impact on vaccination coverage on provinces from the Coast and Highland regions of the country. The pandemic has significantly impacted the immunization programs for infants across Ecuador. This retrospective analysis shows an urgent need to protect vulnerable zones and populations during public health emergencies.