Vaccine-associated Paralytic Poliomyelitis Research Articles

A highly immunogenic UVC inactivated Sabin based polio vaccine.

Despite their efficacy, the currently available polio vaccines, oral polio vaccine (OPV) and inactivated polio vaccine (IPV), possess inherent flaws posing significant challenges in the global eradication of polio. OPV, which uses live Sabin attenuated strains, carries the risk of reversion to pathogenic forms and causing vaccine-associated paralytic poliomyelitis (VAPP) and vaccine-derived polio disease (VDPD) in incompletely vaccinated or immune-compromised individuals. Conventional IPVs, which are non-replicative, are more expensive to manufacture and introduce biohazard and biosecurity risks due to the use of neuropathogenic strains in production. These types of limitations have led to a call by the Global Polio Eradication Initiative and others for the development of updated polio vaccines. We are developing a novel Ultraviolet-C radiation (UVC) inactivation method that preserves immunogenicity and is compatible with attenuated strains of polio. The method incorporates an antioxidant complex, manganese-decapeptide-phosphate (MDP), derived from the radioresistant bacterium Deinococcus radiodurans. The inclusion of MDP protects the immunogenic neutralizing epitopes from damage during UVC inactivation. The novel vaccine candidate, ultraIPVTM, produced using these methods demonstrates three crucial attributes: complete inactivation, which precludes the risk of vaccine-associated disease; use of non-pathogenic strains to reduce production risks; and significantly enhanced yield of doses per milligram of input virus, which could increase vaccine supply while reducing costs. Additionally, ultraIPVTM retains antigenicity post-freeze-thaw cycles, a testament to its robustness.

Vaccine-associated paralytic poliomyelitis in oral polio vaccine recipients: disproportionality analysis using VAERS and systematic review

ABSTRACT Background Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals. Research design and methods This study aimed to (1) Assess the association between OPV and VAPP using Vaccine Adverse Event Reporting System (VAERS) database (2) Outline patient characteristics and risk factors associated with the occurrence of VAPP in OPV recipients through a systematic review of case reports and case series. A disproportionality analysis was conducted using the data from VAERS, encompassing adverse events reported from 1990 till February 2023. Additionally, we conducted a systematic review of case reports and case series using PubMed, Scopus, and Embase databases. Results The VAERS data revealed 130 VAPP reports among 1,739,903 OPV linked adverse events, with year 2010 reporting the strongest association. The systematic review of 37 studies highlighted VAPP occurrence within 2 months to 4 years post-vaccination, typically with acute flaccid paralysis. Immunodeficiency and perianal abscess emerged as major risk factors. Out of the 37 included studies, 27 showed consistent causal association of VAPP with OPV using WHO-AEFI causality assessment tool. Conclusion The study emphasized the seriousness of VAPP and highlights its association with OPV, identifying immunodeficiency as a prominent contributor to VAPP manifestation.

Exploring the Phenotypic Profile of Acute Flaccid Paralysis: Insights from a Third-Level Pediatric Emergency Room.

Acute Flaccid Paralysis (AFP) in children can stem from a diverse array of potential diagnoses. This retrospective study sought to diagnose children referred to a referral pediatric emergency unit with AFP between 2011 and 2016. The study gathered clinical observations, conducted stool and cerebrospinal fluid analyses, and assessed electrophysiological and imaging data. The present study enrolled 118 fully immunized children with a mean age of 6.09 ± 3.60 years. The most prevalent diagnoses included Guillain-Barré Syndrome (GBS-80 cases), acute viral myositis (20 cases), Transverse Myelitis Syndrome (TMS) (TMS-6 cases), and Vaccine-Associated Paralytic Poliomyelitis (VAPP) (VAPP-6 cases). All these six patients had primary immunodeficiency. Notably, all patients tested negative for poliovirus in stool analyses. This study encountered a unique case of a 2.5-month-old male patient who presented with acute limb motor weakness, along with fever, irritability, new-onset hypotonia, and generalized decreased deep tendon reflexes. Notably, no signs of upper motor neuron involvement were found. The Cerebrospinal Fluid (CSF) analysis was compatible with the diagnosis of viral meningitis. Moreover, among the 60 brain and spinal imaging series performed, five were indicative of GBS, six cases showed evidence of TMS, and one revealed a spinal mass. Besides, clinical investigations pointed toward acute viral myositis as a secondary etiology of AFP in 20 patients in this study. In this hospital-based study, the most frequent diagnoses for children arriving at a third-level pediatric Emergency Room (ER) with acute flaccid paralysis AFP were GBS, acute viral myositis, TMS, and VAPP). These findings suggest a distinct pattern of AFP causes compared to those found in community-based epidemiological studies. Additionally, notably, unusual conditions, such as viral meningitis, can rarely present with AFP-like symptoms. Assessment for primary immune deficiency should be considered in cases of VAPP. Lastly, this research has implemented a pediatric AFP Management Protocol: A Local Practical Approach.

Surveillance of acute flaccidparalysis and poliomyelitison some territories of Russia and South Vietnam. Part 1. Polioviruses and paralysis

The epidemiological and etiological aspects of poliomyelitis and acute flaccid paralysis (AFP) in Russia and Vietnam were analysed and compared. The polio-free status is maintained on 14 territories of Russia and 29 provinces of South Vietnam. The quality of epidemiological and virological surveillance for acute flaccid paralysis is in accordance with the requirements of the national and international polio surveillance systems. All AFP cases were revealed, registered, reported and investigated in both countries. The percentage of poliovirus isolation from 2492 samples collected from patients with acute flaccid paralysis and contact persons in different years in Russia ranged from 1.30.89 to 9.80.79. In South Vietnam, 2143 samples from patients with acute flaccid paralysis were investigated. In Russia and Vietnam, we isolated vaccine polioviruses of all three types with predominance of type 3 polioviruses (63% and 50%, respectively) in both countries. From AFP patients in Russia and Vietnam, polioviruses were isolated in 4.9% and 1.0% studied samples, respectively. Some VDPV strains were revealed on the territories of Russia and South Vietnam. Here, we describe five cases of vaccine-associated paralytic poliomyelitis registered in Russia and two cases of AFP caused by VDPV type 2 reported in Vietnam. To prevent the risk of developing vaccine-associated paralytic poliomyelitis, it is indispensable to ensure high-quality surveillance for acute flaccid paralysis, maintain 95% polio vaccine pediatric coverage and strictly comply with sanitary legislation, including the National Vaccination Schedule when vaccinating children, to improve virological surveillance of polioviruses using classical and new virological and molecular methods and to continue research on poliomyelitis, including development of new safe and effective poliovirus vaccines able to induce both humoral and mucosal immunity. The systematic control of adequate polio vaccination is indispensable in order to prevent transmission of imported wild polioviruses into polio free countries as well as circulation of vaccine-derived polioviruses worldwide.

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.

Cost-effectiveness of various immunization schedules with inactivated Sabin strain polio vaccine in Hangzhou, China.

BackgroundIt is necessary to select suitable inactivated poliovirus vaccine(IPV) and live, attenuated oral poliovirus vaccine (OPV) sequential immunization programs and configure the corresponding health resources. An economic evaluation was conducted on the sequential procedures of Sabin strain-based IPV (sIPV) and bivalent OPV (bOPV) with different doses to verify whether a cost-effectiveness target can be achieved. This study aimed to evaluate the cost-effectiveness of different sIPV immunization schedules, which would provide convincing evidence to further change the poliovirus vaccine (PV) immunization strategies in China.MethodsFive strategies were included in this analysis. Based on Strategy 0(S0), the incremental cost (IC), incremental effect (IE), and incremental cost-effectiveness ratio (ICER) of the four different strategies (S1/S2/S3/S4) were calculated based on the perspective of the society. Seven cost items were included in this study. Results of field investigations and expert consultations were used to calculate these costs.ResultsThe ICs of S1/S2/S3/S4 was Chinese Yuan (CNY) 30.77, 68.58, 103.82, and 219.82 million, respectively. The IE of vaccine-associated paralytic poliomyelitis (IEVAPP) cases of S1/S2/S3/S4 were 0.22, 0.22, 0.22, and 0.11, respectively, while the IE of disability-adjusted life-years (IEDALY) of S1/S2/S3/S4 were 8.98, 8.98, 8.98, and 4.49, respectively. The ICERVAPP of S1/S2/S3/S4 gradually increased to CNY 13.99, 31.17, 47.19, and 199.83 million/VAPP, respectively. The ICERDALY of S1/S2/S3/S4 also gradually increased to CNY 0.34, 0.76, 1.16, and 4.90 million/DALY, respectively.ConclusionICERVAPP and ICERDALY were substantially higher for S3 (four-sIPV) and S4 (replacement of self-funded sIPV based on one-sIPV-three-bOPV). Two-sIPV-two-bOPV had a cost-effectiveness advantage, whereas S2/S3/S4 had no cost-effectiveness advantage.

Genetic Characterization of Novel Oral Polio Vaccine Type 2 Viruses During Initial Use Phase Under Emergency Use Listing - Worldwide, March-October 2021.

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL.

Untranslated region-5’ and viral protein 1-based genetic stability analysis of bulk polio in Indonesia 2010-2019

Cases of vaccine-associated paralytic poliomyelitis (VAPP) continued increasingly from 2010-2019 in the world. Oral polio vaccine (OPV) is the live attenuated virus-based vaccine that could genetically revert to neurovirulent during the vaccine production process or when the virus replicates in the human body. The poliovirus neurovirulence is determined by the UTR-5' region and VP1 coding region. UTR-5' played a role in protein translation and VP1 was responsible for the immunogenicity of the virus. Some reported mutations in UTR-5' and VP1 could affect the neurovirulence of poliovirus. In this study, we analyzed the genetic stability of the UTR-5' and VP1 in the bulk of OPV types -1 and -3 produced in 2010 - 2019. The results of the analysis of UTR-5' sequences in Sabin strain types-1 and -3 and VP1 sequences on Sabin virus type 1 did not show any mutations. Meanwhile, the VP1 sequences in Sabin strain type 3 showed nucleotide mutation C2493U that caused the substitution amino acid Thr6Ile amino acid in all samples of the type 3 bulk polio test. Based on the results of in silico analysis, this mutation in VP1 did not contribute significantly to the neurovirulence of the virus.

Enlightment of routine vaccination under the prevention and control of COVID-19 based on the circulating event of type Ⅲ vaccine-derived poliovirus in Shanghai

Since the Global Polio Eradication Initiative was launched by the World Health Assembly in 1988, significant progress has been made in global polio prevention and control. But the occurrence of vaccine-associated paralytic poliomyelitis cases and vaccine-derived poliovirus related cases have become a major challenge during the post-polio era. While coronavirus disease 2019(COVID-19) has brought serious disease burden and economic burden to all countries in the world, prevention and control of vaccine-preventable infectious diseases such as polio should not be neglected under the background of the global common fight against COVID-19. Taking the type Ⅲ VDPV cycle event in Shanghai as an example, the paper discussed how to do a good job of routine inoculation under the prevention and control of COVID-19 to strictly prevent the outbreak of vaccine-preventable infectious diseases.

Poliomyelitis

Wild poliovirus (WPV) comprises 3 serotypes (1, 2, 3) which may infect and destroy spinal cord lower motor neurons. PV is shed via salivary droplets and feces, and it is transmitted person-to-person. One case of polio occurs following ~200 (WPV type 1) to ~1000 (type 2 or 3) WPV infections. Thus, one case is the tiny “tip of the iceberg” of widespread infection. Infection induces long-lasting type-specific immunity, protecting from risk of disease when re-infected, but not from re-infection per se. In low-income countries, polio occurs early in life and immunity plateaus at 5 years of age with almost 100%; in richer countries the age of polio has shifted towards older ages since the 1940s. While the majority of WPV-infected persons remain asymptomatic a small proportion has short fever with upper respiratory or gastrointestinal symptoms. In a few subjects, this first phase may be followed by an acute onset of paralysis of skeletal muscles, due to loss of lower motor neurons from PV infection (=poliomyelitis) with a case-fatality rate of 5%–20%; bulbar involvement increases risk of death, cortical functions (other than emotional, due to physical deformity/disability) are unaffected. Recurrence of pain and worsening of residual motor power may occur 3–4 decades later ("post-polio syndrome"). With no specific treatment available, prevention with one of 2 basic vaccine types (live = oral polio vaccines (OPV); and inactivated (IPV) whole virus vaccine) is of highest importance. With IPV, 3 primary doses and one booster protect nearly 100%, whereas 2 priming and 1 booster doses are sufficient, provided the first dose is given at or after 8 weeks of age and second dose again at or after 8 weeks and one booster at least 6 months after the previous dose. OPV is given orally to induce systemic and gut mucosal immunity, following intestinal infection by vaccination. In the USA and in most temperate regions one dose induces protective immunity in ~75% of subjects against the 3 virus types and the immunity gap is closed by 2 additional doses. In tropical/developing countries vaccine efficacy is as low as ~10% for types 1 or 3 and it may take 10-15 doses to induce immunity in >90%. While there are no safety concerns with IPV, with OPV attenuating mutations may revert, rarely resulting in “vaccine-associated paralytic poliomyelitis” (VAPP), clinically indistinguishable from WPV-caused polio. VPV can spread and cause VAPP in susceptible contacts. In under-vaccinated communities VPV may circulate, mutate, become WPV-like highly transmissible, and even cause outbreaks of polio. Such virus variants are called circulating Vaccine-derived polioviruses (cVDPVs). In the 2020s, only 2 countries continue to have indigenous transmission of WPV 1. Transmission of WPV type 2 had been globally interrupted in 1999 and WPV type 3 in 2012. Nearly all rich countries have abandoned OPV in favor of IPV in order to avoid VAPP. cVDPV type 2 and cVDPV type 1, in their order of frequency, are now the major causes of polio outbreaks in African and Asian countries

Immunization Against Poliomyelitis and the Challenges to Worldwide Poliomyelitis Eradication.

Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed countries despite possessing different vaccine properties. Due to cost, ease of use, and other properties, the Expanded Programme on Immunization added OPV to the routine infant immunization schedule for low-income countries in 1974, but variable vaccine uptake and impaired immune responses due to poor sanitation limited the impact. Following launch of the Global Polio Eradication Initiative in 1988, poliomyelitis incidence has been reduced by >99% and types 2 and 3 wild polioviruses are now eradicated, but progress against type 1 polioviruses which are now confined to Afghanistan and Pakistan has slowed due to insecurity, poor access, and other problems. A strategic, globally coordinated replacement of trivalent OPV with bivalent 1, 3 OPV in 2016 reduced the incidence of vaccine-associated paralytic poliomyelitis (VAPP) but allowed the escape of type 2 vaccine–derived polioviruses (VDPV2) in areas with low immunization rates and use of monovalent OPV2 in response seeded new VDPV2 outbreaks and reestablishment of type 2 endemicity. A novel, more genetically stable type 2 OPV vaccine is undergoing clinical evaluation and may soon be deployed prevent or reduce VDPV2 emergences.

Cost-Effectiveness of Three Poliovirus Immunization Schedules in Shanghai, China.

In Shanghai, China, a polio immunization schedule of four inactivated polio vaccines (IPV) has been implemented since 2020, replacing the schedules of a combination of two IPVs and two bivalent live attenuated oral polio vaccines (bOPV), and four trivalent live attenuated oral polio vaccines (tOPV). This study aimed to assess the cost-effectiveness of these three schedules in infants born in 2016, in preventing vaccine-associated paralytic poliomyelitis (VAPP). We performed a decision tree model and estimated incremental cost-effectiveness ratio (ICER). Compared to the four-tOPV schedule, the two-IPV-two-bOPV schedule averted 1.2 VAPP cases and 16.83 disability-adjusted life years (DALY) annually; while the four-IPV schedule averted 1.35 VAPP cases and 18.96 DALY annually. Consequently, ICERVAPP and ICERDALY were substantially high for two-IPV-two-bOPV (CNY 12.96 million and 0.93 million), and four-IPV (CNY 21.24 million and 1.52 million). Moreover, net monetary benefit of the two-IPV-two-bOPV and four-IPV schedules was highest when the cost of IPV was hypothesized to be less than CNY 23.75 or CNY 9.11, respectively, and willingness-to-pay was hypothesized as CNY 0.6 million in averting one VAPP-induced DALY. IPV-containing schedules are currently cost-ineffective in Shanghai. They may be cost-effective by reducing the prices of IPV, which may accelerate polio eradication in Chinese settings.

Adverse events following immunization with bivalent oral poliovirus vaccine in Jiangsu, China.

The bivalent oral poliovirus vaccine (bOPV; Sabin types 1 and 3) replaced the trivalent OPV (Sabin types 1, 2 and 3) globally in April 2016. A routine schedule of 1 dose of inactivated poliovirus vaccine and 3 subsequent doses of bOPV was implemented in Jiangsu simultaneously. The schedule was changed to 2 inactivated poliovirus vaccines + 2 bOPV on 1 September 2019. Although OPV type 2 has been removed, challenges persist because of adverse events following immunization (AEFIs) with bOPV. Therefore, we analysed and evaluated the safety profile of bOPV administered in children based on passive postmarketing AEFI surveillance. We collected all bOPV-related AEFI reports in Jiangsu from the Chinese National AEFI Information System (CNAEFIS) between May 2016 and April 2020. We obtained the administered doses of bOPV from the Jiangsu Provincial Electronic Immunization Registries System. A descriptive analysis was performed. In total, 2084 bOPV-related AEFIs were retrieved from the CNAEFIS. The overall reporting rate was 24.16 per 100 000 doses. Most AEFIs were nonserious. The most frequently reported symptoms were fever, rash and gastrointestinal disorders. Only 1.34% of AEFIs were serious, which thrombocytopenic purpura accounted for the largest category. Seventeen serious adverse events, including 2 vaccine-associated paralytic poliomyelitis (VAPP) cases, were considered to be related to bOPV vaccination. The rate of VAPP was 0.2 per million doses. AEFI analysis showed that bOPV was well tolerated. The events most frequently reported were nonserious. However, bOPV can still cause VAPP. Attention should be given to risks related to bOPV.

Snake Eye Appearance; A Rare Radiology Presentation in Acute Flaccid Paralysis: A Case Report

Background: Acute flaccid paralysis (AFP) is defined by the acute onset of weakness or paralysis with reduced muscle tone in children. There are many non-infectious and infectious causes. Snake eye appearance (SEA) is a rare radiologic appearance and helps narrow down differential diagnoses in flaccid paralysis. Case Presentation: Here, we reported a 6 months-old girl who was admitted with sudden onset flaccid paralysis. She was lethargic and ill without any detectable deep tendon reflexes. She had a high fever that had started 3 days earlier with malaise, poor feeding and coryza. The first child of the family was a boy who expired with similar symptoms; however, the reason is still unknown. Her parents were relatives (cousins). The laboratory and cerebrospinal fluid tests analysis were normal. The brain MRI analysis revealed T1 dim Hypo intensity and T2 hyperintensity along with obvious ADC map hyperintensity in the brain stem. At first, the PCR tests analysis of stool samples for poliovirus and enterovirus were normal. Spinal MRI showed snake eye appearance and helped us narrow our differential diagnosis. We repeated the PCR tests of stool because of snake eye appearance in cervical MRI that was positive for poliovirus and indicated vaccine-associated Paralytic Poliomyelitis (VAPP). Unfortunately, she expired from vaccine associated poliomyelitis. Conclusion: Snake eye appearance is a rare radiologic appearance that can be seen in several pathological conditions; however, it is very rare in patients with acute flaccid paralysis. Radiology signs, especially in spinal cord MRI, can help recognizing abnormalities in images, and narrow the list of differential diagnosis in acute flaccid paralysis. Therefore, spinal cord MRI has an important role in the evaluation of patient with brain stem involvement in acute flaccid paralysis.

Fractional-dose IPV in polio eradication

The development of fractional-dose inactivated poliovirus vaccine (fIPV) has been crucial to the global polio eradication initiative (GPEI) in the past decade, providing a dose-stretching and affordable option to enable global inactivated poliovirus vaccine (IPV) introduction. In April, 2016, the type 2 component of oral poliovirus vaccine (OPV) was withdrawn from routine immunisation because of the risk of vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the trivalent OPV was replaced with a bivalent form.

Stool Serology: Development of a Non-Invasive Immunological Method for the Detection of Enterovirus-Specific Antibodies in Congo Gorilla Faeces.

Background: The incidence of poliovirus has been significantly reduced by as much as 99.9% globally. Alongside this, however, vaccine-associated paralytic poliomyelitis has emerged. Previously, our team reported in the Lésio-Louna-Léfini Nature Reserve (Republic of Congo) the presence of a new Enterovirus C (Ibou002) in a male gorilla that was put away because of clinical symptoms of facial paralysis. This new virus, isolated was from the stool samples of this gorilla but also from the excrement of an eco-guardian, is very similar to Coxsackievirus (EV-C99) as well as poliovirus 1 and 2. We hypothesised that these symptoms might be due to poliovirus infection. To test our hypothesis, we developed and optimised a non-invasive immunoassay for the detection of Enterovirus-specific antibodies in gorilla faeces that could be useful for routine serosurveillance in such cases. Methods: In order to assess the potential role of poliovirus infection, we have developed and optimised a protocol, based on the lyophilisation and solubilisation of small volumes of stool extracts from 16 gorilla and 3 humans, to detect specific antibodies by western blot and ELISA. Results: First, total immunoglobulins were detected in the concentrated stool extracts. Specific antibodies were then detected in 4/16 gorilla samples and 2/3 human samples by western blot using both the polio vaccine antigen and the Ibou002 antigen and by ELISA using the polio vaccine antigen. Humoral responses were greater with the Ibou002 antigen. Conclusion: We therefore suggest that this recombinant virus could lead to a polio-like disease in the endangered western lowland gorilla. The development of a non-invasive approach to detect microorganism-specific immunoglobulins from faecal samples opens numerous prospects for application in zoonotic infectious diseases and could revolutionise the screening of animals for important emerging infections, such as Ebola fever, rabies and coronavirus infections.

Polio-like deformity: a diagnostic dilemma

ABSTRACT BACKGROUND: Significant advances have been made in the global effort to eradicate polio. Vaccine-associated poliovirus, or other enteroviruses, may still affect the anterior horn cell and cause acute flaccid paralysis. Following the acute disease, residual paralysis results in lower motor neuron weakness, altered growth and deformity. Our study aims to describe the clinical manifestations of a group of children that mimic that of classic paralytic poliomyelitis METHODS: We identified six children from our paediatric orthopaedic database that presented with polio-like deformities. Their clinical and imaging records were reviewed and described, together with the clinical manifestations of paralytic poliomyelitis RESULTS: Limb hypoplasia, pathological gait patterns and foot deformities were consistent features. The median leg length discrepancy was 2.5 cm (range 2-4 cm). The gait patterns observed included a Trendelenburg gait in 33% (n=2), a short limb gait in 50% (n=3), and one case with a combination of Trendelenburg, short limb and steppage gait. Tensor fascia lata contracture was present in 50% (n=3) of our patients. Foot deformities ranged from calcaneo-cavo-valgus to equino-cavo-varus deformities CONCLUSION: Despite significant advances made in the global fight to eradicate polio, we still see children with clinical manifestations reminiscent of the disease. Orthopaedic surgeons should remain familiar with the assessment and diagnosis of the sequelae of paralytic poliomyelitis Level of evidence: Level 5 Keywords: poliomyelitis, vaccine-associated paralytic poliomyelitis, polio-like deformity, acute flaccid paralysis

The Pathology of Poliomyelitis and the Vaccines and Nonvaccine Therapy

Poliomyelitis is an exclusively human disease that mainly affects children. Clinical features of poliomyelitis can be varied, from mild illness to the most severe paralysis, and the factor why poliomyelitis has different performances in individuals has been proved strongly correlated with membrane protein CD155. The nervous system shows a special protecting phenomenon against the invasion of poliovirus, and the mechanism is not very clear at present. Vaccines are the main means of preventing and controlling polio, and many different vaccines have been invented in the process of fighting polio. Inactivated polio vaccine (IPV) and oral polio vaccine (OPV) are the two main vaccines. IPV is known for its safety while OPV is widely used in developing countries because of its relatively low cost. This usage also leads to some side effects: vaccine-associated paralytic polio (VAPP) and vaccine-derived poliovirus (VDPV). Now, for polio eradication, the elimination of these two diseases has become particularly important. Thus, a new type of vaccine was created: sequential IPV-OPV with the safety of IPV and the low cost of OPV. This paper will talk about the different polio vaccines and their effects. An enormous difference between people who have gotten the vaccine and people who have not got the vaccine. Comparing the two kinds of people, people who get normal poliovirus, and people who get poliovirus after taking a vaccine, known as VAPP (vaccine-associated paralytic poliomyelitis), the former cannot get full recovery whole life and the latter has a very low possibility. In conclusion, people should take vaccines if it is affordable for them.

Expected RATE of Vaccine-Associated Paralytic Poliomyelitis: A Simulation Analysis Regarding Transition from the Trivalent to Bivalent Oral Poliovirus Vaccine.

Dear Editor, Poliomyelitis is a preventable infection by vaccine. At present, natural disease exists in some countries, especially those in Africa. The vaccine‑associated paralytic poliomyelitis (VAPP) is an unwanted adverse event of vaccination.

Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in children and infants: two clinical trials

SummaryBackgroundContinued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants.MethodsWe did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1–4 years) and infants (aged 18–22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ClinicalTrials.gov, NCT02521974 and NCT03554798.FindingsThe control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medical events in any group. Solicited and unsolicited adverse events were overwhelmingly mild or moderate irrespective of vaccine or dose. Nearly all children were seroprotected at baseline, indicating high baseline immunity. In children, the seroprotection rate 28 days after one dose was 100% for monovalent OPV2 and both novel OPV2 candidates. In infants at day 28, 91 (94% [95% CI 87–98]) of 97 were seroprotected after receiving monovalent OPV2, 134 (94% [88–97]) of 143 after high-dose novel OPV2-c1, 122 (93% [87–97]) of 131 after low-dose novel OPV2-c1, 138 (95% [90–98]) of 146 after high-dose novel OPV2-c2, and 115 (91% [84–95]) of 127 after low-dose novel OPV2-c2. Non-inferiority was shown for low-dose and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 despite monovalent OPV2 recipients having higher baseline immunity.InterpretationBoth novel OPV2 candidates were safe, well tolerated, and immunogenic in children and infants. Novel OPV2 could be an important addition to our resources against poliovirus given the current epidemiological situation.FundingFighting Infectious Diseases in Emerging Countries and Bill & Melinda Gates Foundation.