• Vol. 52 No. 1, 17–26
  • 30 January 2023

Combating a resurgence of poliomyelitis through public health surveillance and vaccination

ABSTRACT

Poliomyelitis, or polio, is a highly infectious disease and can result in permanent flaccid paralysis of the limbs. Singapore was certified polio-free by the World Health Organization (WHO) on 29 October 2000, together with 36 other countries in the Western Pacific Region. The last imported case of polio in Singapore was in 2006. Fortunately, polio is vaccine-preventable—the world saw the global eradication of wild poliovirus types 2 and 3 achieved in 2015 and 2019, respectively. However, in late 2022, a resurgence of paralytic polio cases from vaccine-derived poliovirus (VDPV) was detected in countries like Israel and the US (specifically, New York); VDPV was also detected during routine sewage water surveillance with no paralysis cases in London, UK. Without global eradication, there is a risk of re-infection from importation and spread of wild poliovirus or VDPV, or new emergence and circulation of VDPV. During the COVID-19 pandemic, worldwide routine childhood vaccination coverage fell by 5% to 81% in 2020–2021. Fortunately, Singapore has maintained a constantly high vaccination coverage of 96% among 1-year-old children as recorded in 2021. All countries must ensure high poliovirus vaccination coverage in their population to eradicate poliovirus globally, and appropriate interventions must be taken to rectify this if the coverage falters. In 2020, WHO approved the Emergency Use Listing of a novel oral polio vaccine type 2 for countries experiencing circulating VDPV type 2 outbreaks. Environmental and wastewater surveillance should be implemented to allow early detection of “silent” poliovirus transmission in the population, instead of relying on clinical surveillance of acute flaccid paralysis based on case definition alone.


Singapore was certified poliomyelitis (polio)-free by the World Health Organization (WHO) on 29 October 2000, together with 36 other countries in the Western Pacific Region.1 Prior to certification, there were multiple outbreaks in 1958, 1960 and 1963 with 415, 196 and 74 paralytic polio cases, respectively.2-4 The nationwide immunisation programme in Singapore using the oral poliovirus vaccines (OPV) led to a marked decrease in outbreaks of polio. No case of indigenous polio was reported from 1978 onwards.1 The last imported case of polio in Singapore was in 2006 when a 2-year-old Nigerian girl presented with left lower limb paralysis and her stool was positive for wild poliovirus (WPV) type 1.5

In this review, we seek to provide an update on the clinical manifestations of polio, other infections that can mimic polio, and the history of poliovirus vaccination. We also describe the status of global eradication efforts since the COVID-19 pandemic and highlight key public health interventions necessary to mitigate the risk of poliovirus outbreaks globally.

Characteristics of poliovirus

“Poliomyelitis” originates from the Greek words ‘‘polio’’ and ‘‘myelon’’, which mean “grey” and “marrow”, respectively, due to its effect on the spinal cord. It is a highly infectious disease caused by one of the three poliovirus serotypes (poliovirus types 1, 2 or 3), belonging to the Enterovirus genus and Picornaviridae family.6 Poliovirus can survive in the environment (soil and water) for months at 4°C, but viral infectivity can be reduced by heating. Poliovirus is resistant to common detergents and lipid solvents, but can be inactivated by formaldehyde, heat or chlorine.6,7

 Humans are the only reservoir for poliovirus, and it can be transmitted from a symptomatic or asymptomatic carrier via the faecal-oral or oral-oral route. Transmission can also occur through close contact via oral exposure to cough or sneeze droplets. The faecal-oral route is more common in areas with poor sanitation, especially among the non-immune population. Poliovirus is most contagious from 7–10 days before and after the onset of symptoms.8 Immunocompetent infected persons can shed poliovirus in the pharynx and stools for around 2 and 4 weeks, respectively.8 In contrast, immune-compromised persons can shed the virus for a longer period of time, with a median length of excretion of 1.3 years.9 The development of mucosal immune responses in the form of immunoglobulin A is associated with a decrease in viral replication, shedding and risk of transmission.10,11 Hence, persons with deficiencies in mucosal immune responses are at higher risk of prolonged poliovirus shedding and viral transmission.10,11

Clinical presentation of poliomyelitis

The poliovirus enters through the oral route and multiplies in the oropharynx, tonsils, cervical lymph nodes and gastrointestinal tract. In the gastrointestinal tract, the virus can invade lymphoid tissue; it may enter the bloodstream to infect the central nervous system, causing the destruction of motor neurons.

Poliovirus can lead to one of the following disease manifestations: (1) asymptomatic infection; (2) abortive polio or minor illness; (3) non-paralytic polio or aseptic meningitis; or (4) paralytic polio, which is the most severe presentation. Table 1 summarises the characteristics of each disease manifestation.6,7,12-19 Paralytic polio is extremely rare and seen in <1% of poliovirus infections. Therefore, the detection of a single case of polio will suggest wider unknown transmission in the population. Patients can present with severe back, neck and muscle pain associated with involvement of the spinal, mixed spinal-bulbar or bulbar paralysis. Bulbar polio has the highest mortality due to the involvement of the brainstem neurons. Involvement of the respiratory muscles can also lead to death. Polioencephalitis can also occur where patients present with confusion and seizures with upper motor neuron signs, which are indistinguishable from other viral encephalitis.17 Sensory involvement never occurs in polio.

Table 1. Summary of clinical manifestations of poliovirus infection6,7,12-19

In children and rarely in adults, paralytic spinal polio can present classically with a biphasic course. This course is an initial period of minor illness followed by a brief symptom-free period of up to 10 days and subsequent rapid onset of acute flaccid paralysis (AFP) with asymmetrical paralysis, loss of deep tendon reflexes, fever, headache, neck stiffness and cerebrospinal fluid (CSF) pleocytosis.13,14 Recovery may occur in some patients. In around 50% of the survivors of paralytic polio, a non-infectious post-polio syndrome (PPS) can occur 8–71 years later.7 A new gradual onset of muscle weakness, pain and fatigue can occur in the same muscles that were affected during the course of paralytic spinal polio. Previously unaffected limb muscle groups can also be involved in PPS.

Other infectious aetiologies of AFP

AFP is a clinical syndrome characterised by an acute onset of flaccid limb weakness of <4 weeks, which can also involve the respiratory and/or swallowing muscles. Progression to maximum severity can occur within days to weeks. Other infectious aetiologies of AFP that have been described include non-polio enterovirus D68 and A71, flavivirus and human herpesvirus. Table 2 summarises the characteristics of other infections that can lead to AFP.20-26 As poliovirus is only one of the causes of AFP, and there are other infections and immune-mediated syndromes that can mimic polio, WHO uses a screening case definition for surveillance of AFP to evaluate polio outbreaks.12 This definition includes any case of AFP in children aged <15 years old, or a person of any age where polio is suspected. Clinical vigilance in notifying health authorities early about patients who fulfil the AFP case definition is important, as part of efforts to eradicate polio.

Table 2. Summary of other infectious aetiologies that can lead to polio-like illness20-26

Diagnosis of poliomyelitis

Poliovirus can be detected by isolating the virus in cell culture from isolates of stool, throat swabs, blood, CSF or by polymerase chain reaction (PCR).8,12 Viral culture or PCR from stool isolate is the most sensitive diagnostic method given the prolonged stool viral shedding. Isolation of the virus is also more common in pharyngeal specimens than blood or CSF. Viral isolates can subsequently undergo genome sequencing to aid in the identification of the poliovirus serotype, and differentiate between wild-type and vaccine (Sabin)-derived infection. Two samples of stool collected at least 24 hours apart within 2 weeks of symptom onset can further increase the sensitivity of the tests.27 In the absence of isolates, paired acute and convalescent blood serum (with a 4-fold increase in titre during the convalescent phase) for neutralising antibodies against the three poliovirus serotypes can diagnose polio in the presence of clinical symptoms and/or epidemiological risk factors for polio. However, serologic tests cannot differentiate between wild-type and vaccine-derived polio.

Management of poliomyelitis

Currently, there is no antiviral medication for the treatment of polio. A capsid inhibitor, pocapavir, had completed a phase 1 trial and was shown to be safe and effective in improving viral clearance in immunocompromised persons.28 However, there was a concern about emerging viral resistance in a group of study patients in the isolation facility.28 The study was not able to accurately conclude if pocapavir had led to viral resistance directly. More studies are required to evaluate if pocapavir can indeed lead to drug resistance in immunocompromised persons and if proven so, other drug combinations may be required to overcome the resistance.

For persons who suffer from paralytic polio, various supportive management strategies including mechanical ventilation, pain management with analgaesia, neurorehabilitation and use of orthotic devices have been deployed to maximise recovery and improve outcomes.

History of poliovirus vaccinations

Historically, the first available polio vaccine was the inactivated poliovirus vaccine (IPV), which was created in the 1950s and licensed in 1955. IPV was available as the trivalent form containing the three poliovirus (PV) serotypes PV1, PV2 and PV3. OPV was initially available as a monovalent form in 1961, followed by the trivalent form (tOPV) in 1963.12 Both IPV and OPV provide substantial immunity and protection against polio, but only OPV provides intestinal immunity, while IPV provides some nasopharyngeal immunity.29 OPV contains live Sabin poliovirus strains, which are derived from WPV strains attenuated by multiple passages in non-human cell culture, hence reducing neurovirulence and transmissibility.30 While the attenuated PV did not cause disease, it replicated sufficiently to induce protective immunity. However, vaccine-derived poliovirus (VDPV) can undergo genetic changes during replication, such as in reversing the mutations in the viral genome that conferred the attenuation phenotype, and/or acquiring new mutations with enhanced neurovirulence.31,32 Since the VDPV in OPV can shed for several weeks in the oropharyngeal secretions and stools post-vaccination, the transmission of these viruses from a vaccinated person can lead to vaccine-derived paralytic polio (VDPP). VDPP is clinically identical to the paralysis caused by wild poliovirus but is a rare adverse event of OPV on its recipients and particularly, unvaccinated contacts.

The national immunisation schedule in Singapore had an all-OPV schedule comprising 6 doses of tOPV until June 2013. This was replaced with a sequential IPV-OPV schedule comprising the recommendation for 4 IPV doses given at ages 3, 4 and 5 months, with a booster dose at 18 months. A fifth dose of tOPV at 10–11 years old (primary school level 5) was recommended. The tOPV dose at 6–7 years old (primary school level 1) was discontinued at the end of 2013.

WPV type 2 virus has not been detected since 1999 and was declared to be eradicated in September 2015.12 Consequently, WHO removed serotype 2 from tOPV in a global synchronised switch and replaced it with the bivalent OPV (bOPV) containing types 1 and 3 Sabin viruses. This became the only globally available OPV from May 2016. Monovalent OPV containing serotype 2 is only stockpiled for emergency or outbreak use.

Global eradication of WPV type 3 was declared on 24 October 2019.12 Since 2020 when bOPV was no longer available, the national immunisation schedule in Singapore changed to an all-IPV schedule using the 5-in-1 vaccine (DTaP-IPV-Hib: against diphtheria, tetanus, acellular pertussis, inactivated polio and Haemophilus influenzae type b) or the 6-in-1 vaccine (DTaP-IPV-Hib-HepB: 5-in-1 and against hepatitis B) given at age 2, 4 and 6 months (schedule revised from 3, 4 and 5 months since 1 November 2020) followed by the fourth dose of 5-in-1 vaccine at 18 months. The fifth dose of IPV at age 10–11 years is given as a combined tetanus, diphtheria, pertussis, polio and IPV vaccine, i.e. Tdap-IPV (Adacel-Polio or Boostrix-Polio), to supplement waning immunity over time. The waning immunity effect was seen in a study from Sri Lanka whereby PV3 seropositivity was reduced to 75% among 15-year-old children despite 5 doses of OPV.33 In another study, protective antibodies against all three serotypes persisted for at least 18 years after the administration of the last dose of OPV or IPV, with a longer duration of immunity against PV3 provided by IPV as compared to OPV.34 The last seroprevalence study in Singapore conducted from 2008–2010 showed that approximately 92.3% of children aged 1–17 years had antibodies against poliovirus.35

In Singapore, the infant vaccination rate (3 completed doses) for polio was 96.5% in 2018 and fairly stable (96.3–96.9%) from 2014–2018. However, the first booster dose completion in 2-year-olds decreased from 90–91% in 2014–2017 to 89.3% in 2018.36 The lowest reported first booster uptake was 83% in 2003, after which it hovered at 87–91% in 2004–2010.1 The first booster completion rates showed a worrying trend for uptake of dose at age 18 months. In addition, the booster dose uptake at 10–11 years old (primary school level 5) decreased from 97.4% in 2016–2017 to 95.2% in 2018.36 Reassuringly, a local review of vaccination records extracted in November 2020–December 2021 from SingHealth polyclinics showed an improvement in vaccine uptake by 10.8% (an increase from 65.9 to 76.7%) of children at 6 months old and 2.1% (from 58.9 to 61.0%) at 12 months old after the revision from 3, 4 and 5 months to 2, 4 and 6 months.37 Another study showed that during the COVID-19 pandemic from January–April 2020, there was a 0.4–10.3% drop in 5-in-1 vaccine uptake compared to January–April 2019.38 After the “circuit breaker” period from 7 April–1 June 2022, routine childhood vaccinations reverted to levels from pre-COVID-19 pandemic, reflecting a temporary postponement in vaccination due to the pandemic.39

In 2020, WHO approved the Emergency Use Listing of a novel OPV type 2 (nOPV2) vaccine for countries experiencing circulating VDPV type 2 (cVDPV2) outbreaks.40 The vaccine is a modified version of type 2 monovalent OPV that showed comparable protection against poliovirus in clinical trials while being more genetically stable and did not revert to virulence.41-43 Currently, the nOPV2 vaccine is only deployed in cVDPV2 outbreaks and not for routine use globally. Available safety data on the first 65 million doses of nOPV2 use for outbreak response showed that there were no safety concerns.12

Re-emergence of poliovirus and public health response

In 1988, WHO established the Global Polio Eradication Initiative with the aim of achieving polio eradication by the year 2000.12,44 The last cases of WPV type 2 were reported in 1999 in India, and WPV type 3 in 2012 in Nigeria.12 Despite most countries being certified polio-free, polio was declared a Public Health Emergency of International Concern by WHO in 2014 with outbreaks in certain countries.12 In the absence of global eradication, the risk of re-infection from the importation of wild or VDPV from another country or emergence and circulation of VDPV remains.

In 2015, WPV type 2 was officially declared to be eradicated. The following year, there was a global switch from tOPV to bOPV (type 1 and type 3 only) to remove the risk associated with the ongoing use of live-attenuated type 2 vaccine. To address a potential gap in immunity to type 2, one dose of IPV was recommended to coincide with the switch. Unfortunately, the process encountered challenges leading to the emergence of type 2 immunity gaps. In addition, poorly coordinated outbreak responses using monovalent OPV type 2 vaccine inadvertently resulted in the emergence of more VDPV2, especially in areas of low coverage. These issues were further exacerbated by the emergence of SARS-CoV-2 and subsequent COVID-19 pandemic, resulting in disruptions and suspension of supplementary immunisation activity in 2020. In 2021, six WPV type 1 cases were reported in only 2 endemic countries, Afghanistan and Pakistan.45

Relatively recently, Jerusalem, Israel and New York, US reported one case of paralytic polio each in March and July 2022, respectively.46,47 The case in Jerusalem was an unvaccinated child, 3 years and 9 months old, with AFP presenting in February 2022 from whom VDPV type 3 was detected in the stools.46 The case in New York was a young unvaccinated adult who developed AFP and had VDPV type 2 in his stools.47 Prior to his illness, wastewater surveillance in his county and a neighbouring county had detected VDPV 25 days before and 41 days after his onset of illness. He presented with 5 days of low-grade fever, neck stiffness, back and abdominal pain, constipation and 2 days of AFP. He was unvaccinated and had attended a large gathering 8 days before his illness with no international travel. The polio vaccination uptake in his county had been low at 67.0% in July 2020, which decreased to 60.3% in August 2022, with uptake as low as 37.3% in some areas.47 In contrast, the national IPV uptake by 24-month-old children was 92.7% among infants born in 2017–2018.48 In London, UK, sewage and wastewater surveillance also detected VDPV2 from February 2022, with no cases of paralytic polio.49

Table 3. Poliomyelitis in non-endemic countries by type of virus and number of cases reported in 2021/2022 (as of 5 October 2022)50,51

As of 5 October 2022, 33 countries were reported to be affected by poliovirus (Table 3).50,51 These countries had previously stopped local transmission of WPV but now have re-infection or re-emergence of WPV or VDPV. Not surprisingly, VDPV type 2 is the predominant type of poliovirus with WPV type 1 also detected in Malawi and Mozambique. Four countries—Malawi, Mozambique, Yemen and Israel—are affected by more than one virus type. Nigeria, Yemen and the Democratic Republic of the Congo account for the majority of clinical polio cases reported. Therefore, the recent reports of VDPV in New York and London were not unique or new. However, VDPV occurrence across the world may be an indicator of a worrying trend in the global polio eradication effort and a wake-up call for all countries.

To mitigate the risks of transmission and outbreaks, there are a number of key public health interventions all countries will need to focus on regardless of their polio-free status. First, maintaining high vaccination coverage in the population is critical. Global routine childhood vaccination coverage has fallen by 5%—from 86% to 81%—for 3-dose completion of diphtheria-tetanus-pertussis vaccination during the COVID-19 pandemic.52 Transiting out of the COVID-19 pandemic, the ongoing political instability around the world, and the associated increase in global migration are world events that will inevitably facilitate the poliovirus’ movement. Since the withdrawal of tOPV, it is essential that IPV coverage improves to ensure that children are protected against the clinical manifestation of paralytic polio. There is a need to invest in and maintain surveillance systems to enable the early detection of “silent” poliovirus transmission in the population as demonstrated by the events in Israel, the UK and the US. To augment ongoing AFP surveillance, environmental surveillance systems with genomic sequencing capabilities are essential. Such systems need to be working well to ensure cases of polio—and more importantly, “silent” transmissions—in the population are detected quickly to inform public health response. Finally, the recent development and emergency licensing of nOPV2 vaccine is much-welcomed news. The nOPV2 vaccine is genetically more stable and hence, less likely to result in the loss of key attenuation mutations.41,53 Population acceptance and appropriate implementation of nOPV2 will minimise the risk of future seeding events.

CONCLUSION

The potential for clinical disease with significant mortality and morbidity remains for polio in light of the absence of antiviral treatment options. The poliovirus vaccination programme has been critically important to date, and the development of nOPV2 is a much-needed boost to global eradication efforts. Polio has not disappeared as evidenced by the recent resurgence of paralytic polio cases in Israel, the US and other countries, as well as the detection of VDPV in wastewater in London relatively recently. All countries must ensure high poliovirus vaccination coverage in their population, and appropriate interventions must be taken to rectify this if coverage falters. Surveillance systems, including those for the environment and wastewater should be implemented to allow early detection of “silent” poliovirus transmission in the population, instead of relying on AFP surveillance alone.

REFERENCES

  1. Lee HC, Tay J, Kwok CY, et al. Certification of poliomyelitis eradication in Singapore and the challenges ahead. Ann Acad Med Singap 2012;41:518-28.
  2. Hale JH, Doraisingham M, Kanagaratnam K, et al. Large-scale use of Sabin type 2 attenuated poliovirus vaccine in Singapore during a type 1 poliomyelitis epidemic. Br Med J 1959;1:1541-9
  3. Lee LH, Lim KA. Eradication of poliomyelitis in Singapore. Singapore Med J 1977;18:34-40.
  4. Lee LH, Lim KA, Kanagaratnam K. The poliomyelitis immunization programme in Singapore. Singapore Med J 1965;5:89-95.
  5. Ministry of Health, Singapore. Maintaining polio-free certification status in Singapore, 2010. Epidemiol News Bull 2011;37:81-7.
  6. Bodian D, Horstmann DM. Polioviruses. In: Horsfall FL, Tamm I (Eds). Viral and Rickettsial infections of Man. 4th ed. Philadelphia: JB Lippincott Co; 1965:430-73.
  7. Jubelt B, Cashman NR. Neurological manifestations of the post-polio syndrome. Crit Rev Neurobiol 1987;3:199-220.
  8. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Chapter 18: Poliomyelitis. https://www.cdc.gov/vaccines/pubs/pinkbook/polio.html. Accessed 11 October 2022.
  9. Macklin G, Liao Y, Takane M, et al. Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry. Front Immunol 2017;8:1103.
  10. Wright PF, Wieland-Alter W, Ilyushina NA, et al. Intestinal immunity is a determinant of clearance of poliovirus after oral vaccination. J Infect Dis 2014;209:1628-34.
  11. Donlan AN, Petri WA Jr. Mucosal immunity and the eradication of polio. Science 2020;368:362-3.
  12. World Health Organization. Polio vaccines: WHO position paper – June 2022. Weekly Epidemiological Record 2022;97:277-300.
  13. Nathanson N, Kew OM. From emergence to eradication: the epidemiology of polio myelitis deconstructed. Am J Epidemiol 2010;172:1213-29.
  14. McQuillen D, McQuillen M. Poliomyelitis. In: Jones Royden H (Ed). Netter’s Neurology. Philadelphia: Elsevier Saunders; 2005:597-601.
  15. Boyer FC, Tiffreau V, Rapin A, et al. Post-polio syndrome: Pathophysiological hypotheses, diagnosis criteria, drug therapy. Ann Phys Rehabil Med 2010;53:34-41.
  16. Melnick JL. Current status of poliovirus infections. Clin Microbiol Rev 1996;9:293-300.
  17. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th edition (Volume 2). Philadelphia: Elsevier Churchill Livingstone; 2020:2221-3.
  18. Kidd D, Williams AJ, Howard RS. Poliomyelitis. Postgrad Med J 1996;72:641-7.
  19. Halstead LS, Gawne AC, Pham BT. National rehabilitation hospital limb classification for exercise, research, and clinical trials in post-polio patients. Ann N Y Acad Sci 1995;753:343-53.
  20. Holm-Hansen CC, Midgley SE, Fischer TK. Global emergence of enterovirus D68: a systematic review. Lancet Infect Dis 2016;16:e64-75.
  21. Marx A, Glass JD, Sutter RW. Differential diagnosis of acute flaccid paralysis and its role in poliomyelitis surveillance. Epidemiol Rev 2000;22:298-316.
  22. Washington State Department of Health. Acute flaccid myelitis (AFM)/poliomyelitis. https://doh.wa.gov/sites/default/files/legacy/Documents/5100/420-068-Guideline-PolioAFM.pdf?uid=6339ad0d59025. Accessed 6 October 2022.
  23. Petersen LR, Brault AC, Nasci RS. West Nile virus: review of the literature. JAMA 2013;310:308-15.
  24. Solomon T, Kneen R, Dung NM, et al. Poliomyelitis-like illness due to Japanese encephalitis virus. Lancet 1998;351:1094-7.
  25. Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet 2008;371:1861-71.
  26. Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th edition (Volume 2). Philadelphia: Elsevier Churchill Livingstone; 2020: 1828-90, 2238-42, 2911-21, 2954-9.
  27. Cardemil CV, Rathee M, Gary H, et al. Surveillance during an era of rapidly changing poliovirus epidemiology in India: the role of one vs. two stool specimens in poliovirus detection, 2000-2010. Epidemiol Infect 2014;142:163-71.
  28. Collett MS, Hincks JR, Benschop K, et al. Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model. J Infect Dis 2017;215:335-43.
  29. Faden H, Modlin JF, Thoms ML, et al. Comparative evaluation of immunization with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines in childhood: systemic and local immune responses. J Infect Dis 1990;162:1291-7.
  30. Sabin AB, Boulger LR. History of Sabin attenuated poliovirus oral live vaccine strains. J Biol Stand 1973;1:115-8.
  31. Kew OM, Sutter RW, de Gourville EM, et al. Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol 2005;59:587-635.
  32. Famulare M, Chang S, Iber J, et al. Sabin vaccine reversion in the field: a comprehensive analysis of Sabin-like poliovirus isolates in Nigeria. J Virol 2015;90:317-31.
  33. Gamage D, Palihawadana P, Mach O, et al. Achieving high seroprevalence against polioviruses in Sri Lanka – results from a serological survey, 2014. J Epidemiol Glob Health 2015;5(4 Suppl 1):S67-71.
  34. Larocca AMV, Bianchi FP, Bozzi A, et al. Long-Term Immunogenicity of Inactivated and Oral Polio Vaccines: An Italian Retrospective Cohort Study. Vaccines (Basel) 2022;10:1329.
  35. Lai FY, Thoon KC, Ang LW, et al. Comparative seroepidemiology of pertussis, diphtheria and poliovirus antibodies in Singapore: waning pertussis immunity in a highly immunized population and the need for adolescent booster doses. Vaccine 2012;30:3566-71.
  36. Communicable Diseases Division, Ministry of Health, Singapore. Communicable diseases surveillance, Singapore 2018. Chapter 7: Childhood Immunisation. https://www.moh.gov.sg/docs/librariesprovider5/diseases-updates/communicable-diseases-surveillance-in-singapore-2018210c9a3beaa94db49299c2da53322dce.pdf. Accessed 11 October 2022.
  37. Tan NC, Tan Q, Aau WK, et al. The implementation and impact of a revised national childhood immunization schedule in an urban Asian community. Vaccines (Basel) 2022;10:1148.
  38. Zhong Y, Clapham HE, Aishworiya R, et al. Childhood vaccinations: Hidden impact of COVID-19 on children in Singapore. Vaccine 2021;39:780-5.
  39. World Health Organization. Polio (Pol3) immunization coverage among 1-year-olds (%) (WUENIC). https://www.who.int/data/gho/indicator-metadata-registry/imr-details/2443. Accessed 12 December 2023.
  40. World Health Organization. First ever vaccine listed under WHO emergency use, 13 November 2020. https://www.who.int/news/item/13-11-2020-first-ever-vaccine-listed-under-who-emergency-use. Accessed 1 October 2022.
  41. Van Damme P, De Coster I, Bandyopadhyay AS, et al. The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study. Lancet 2019;394:148-58.
  42. De Coster I, Leroux-Roels I, Bandyopadhyay AS, et al. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in healthy adults: two clinical trials. Lancet 2021;397:39-50.
  43. Sáez-Llorens X, Bandyopadhyay AS, Gast C, et al. 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. Lancet 2021;397:27-38.
  44. Celentano LP, Carrillo-Santisteve P, O’Connor P, et al. Global polio eradication: Where are we in Europe and what next? Vaccine 2018;36:5449-53.
  45. World Health Organization. Global Wild Poliovirus 2015–2020. https://polioeradication.org/wp-content/uploads/2021/01/weekly-polio-analyses-WPV-20210119.pdf. Accessed 29 September 2022.
  46. World Health Organization. Circulating vaccine-derived poliovirus type 3 – Israel, 15 April 2022. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON366. Accessed 1 October 2022.
  47. Link-Gelles R, Lutterloh E, Schnabel Ruppert P, et al. Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater – New York, June–August 2022. MMWR Morb Mortal Wkly Rep 2022;71:1065-8.
  48. Hill HA, Yankey D, Elam-Evans LD, et al. Vaccination coverage by age 24 months among children born in 2017 and 2018 – National Immunization Survey-Child, United States, 2018– MMWR Morb Mortal Wkly Rep 2021;70:1435-40.
  49. WisePoliovirus is detected in sewage from north and east London. BMJ 2022;377:o1546.
  50. Global Polio Eradication Initiative, World Health Organization. This Week as of 6 October 2022. https://polioeradication.org/polio-today/polio-now/this-week/. Accessed 6 October 2022.
  51. Our World in Data. Polio. https://ourworldindata.org/polio. Accessed 6 October 2022.
  52. World Health Organization. Covid-19 pandemic fuels largest continued backslide in vaccinations in three decades, 15 July 2022. https://www.who.int/news/item/15-07-2022-covid-19-pandemic-fuels-largest-continued-backslide-in-vaccinations-in-three-decades. Accessed 1 October 2022.
  53. Bandyopadhyay AS, Zipursky S. A novel tool to eradicate an ancient scourge: the novel oral polio vaccine type 2 story. Lancet Infect Dis 2022:S1473-3099(22)00582-5.