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/disabilty) 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

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.

Risk factors for functional deterioration in a cohort with late effects of poliomyelitis: A ten-year follow-up study

BACKGROUND: More than 7000 patients developed poliomyelitis during the main epidemic in the fifties in Israel. In recent years, there is a further deterioration in their condition due to accelerated aging process and post-polio syndrome. OBJECTIVE: To evaluate the risk factors for the progression of functional status in a cohort of patients with late effect of poliomyelitis over a period of ten years. METHODS: A cross-sectional cohort study including 82 individuals with late effect of poliomyelitis evaluated over ten years. Mean age was 67±8.5 years, 52.4%were men and 79.3%were Jewish. Functional status was evaluated by activities of daily living (ADL) questionnaire. Risk factors, including general comorbidities, history of poliomyelitis infection, use of assistive devices, employment, and physical activity statuses were evaluated using specific questionnaires. RESULTS: Independence in ADL functions deteriorated significantly over ten years. Older age, ethnicity, use of a wheelchair, and use of orthotic devices in childhood were risk factors for deterioration in ADL function. No correlation was found between the presence of other comorbidities or poliomyelitis parameters and worsening of ADL functions. CONCLUSIONS: Late effect of poliomyelitis was associated with deterioration in ADL functions probably due to the combined effect of the initial severity of the paralytic poliomyelitis symptoms and accelerated aging.

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.

Poliovirus excretion among children with primary immune deficiency in Pakistan: a pilot surveillance study protocol

IntroductionChildren with primary immunodeficiency disorders (PID) are more susceptible to developing viral infections and are at a substantially increased risk of developing paralytic poliomyelitis. Such children, if given oral polio vaccines tend to excrete poliovirus chronically that may lead to the propagation of highly divergent vaccine-derived poliovirus (VDPV). Consequently, they may act as a reservoir for the community by introducing an altered virus potentially imposing a risk to global polio eradication. However, the risks of chronic and prolonged excretion are not well characterised in the study context. This study seeks to establish a pilot surveillance system for successful identification and monitoring of VDPV excretion among children with PID. It will assess whether the Jeffrey Modell warning signs of PID can be used as an appropriate screening tool for PID in Pakistan.Methods and analysisIn this pilot surveillance, recruitment of PID cases is currently done at participating hospitals in Pakistan. Potential children are screened and tested against the Jeffrey Modell Foundation (JMF) warning signs for immunodeficiency and their stool is collected to test for poliovirus excretion. Cases excreting poliovirus are followed until the two consecutive negative stool samples are obtained over a period of 6 months. The data will be analysed to calculate hospital-based proportions of total Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases over a 2-year period and to determine the sensitivity and specificity of the JMF signs.Ethics and disseminationThis protocol was reviewed and approved by the WHO (WHO Reference-2018/811124-0), Aga Khan University (AKU ERC-2018-0380-1029) and National Bioethics Committee (Ref No. 4-87 NBC-308-Y2). The results will be published in an open access peer-reviewed scientific journal and presented to the iVDPV Working Group members, policy-makers, paediatric consultants and fellow researchers with the same domain interest. It may be presented in scientific conferences and seminars in the form of oral or poster presentations.

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.

The association of online search interest with polio cases and vaccine coverage: an infodemiological and ecological study

Background: Achievement of universal eradication of paralytic poliomyelitis has remained a challenge. Despite the general decline in cases, multiple outbreaks attributed to poor vaccination still occur. Noncompliance from vaccination can be improved through education on various media platforms. In the internet age, online health-seeking behavior plays a significant role in this regard. Hence, our study investigated the association between global online search interest in polio with the number of polio cases and vaccination coverage.Methods: This infodemiological and ecological study utilized Google Trends’ search volume index (SVI) for “polio” and the World Health Organization data on the number of polio cases (PC) and vaccine coverage rate (VCR) per country between 2006 to 2019. Associations between SVI for “polio” with PC and with VCR were evaluated.Results: From the years 2006 to 2019, the global inquiry for this term was highest (i.e., SVI at 100) last October 2018. There is a direct correlation between the SVI for “polio” and PC while there is an inverse relationship between SVI and VCR per country per year. Both relationships have weak- to moderate strength of associations. Based on our models, a one-unit increase in the SVI leads to a 3.8% increase in the number of polio cases. On the other hand, a one-unit increase in the SVI leads to a 0.01% decrease in the VCR. Conclusions: Dynamic changes in global SVIs for polio may reflect fluctuations in the number of polio cases and rates of vaccine coverage. Our study brings into light the largely untapped and potential use of online search behavior for polio to anticipate changes in PC and VCR in real-time.

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.

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

Stool serology: development of a non-invasive immunological method for the detection of Enterovirus-specific antibodies in Congo gorilla faeces

The incidence of poliovirus has significantly reduced by as much as 99.9% globally. Alongside this, however, vaccine-associated paralytic poliomyelitis has emerged. Recently, a new recombinant virus (Enterovirus C/Poliovirus) was identified in humans working as eco-guards and in gorillas in Democratic Republic of Congo, including one gorilla with polio-like sequelae. A strain of this recombinant virus (Ibou002) was also isolated from gorilla faeces. 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, to detect specific antibodies. First, total immunoglobulins was 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. 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 method to detect microorganism-specific immunoglobulins from faecal samples opens up new perspectives for the exploration of humoral responses of pathogens in animals and a greater understanding of zoonotic infectious diseases.