Achieving High Poliovirus Antibody Seroprevalence in Areas at Risk of Vaccine Derived Poliovirus Transmission – Niger Experience

Background Outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across Africa. We conducted a serological survey of polio antibodies in polio high-risk areas of Niger to assess risk of poliovirus outbreaks. Methods Children between 1 and 5 years of age were enrolled from structures randomly selected using satellite imaging enumeration in Diffa Province, Niger in July 2019. After obtaining informed consent, dried blood spot cards were collected. Neutralizing antibodies against three poliovirus serotypes were detected using microneutralization assay at the Centers for Disease Control and Prevention, Atlanta. Results We obtained analysable data from 309/322 (95.9%) enrolled children. Seroprevalence of polio antibodies was 290/309 (93.9%), 272/309 (88.0%), and 254/309 (82.2%) for serotypes 1, 2 and 3 respectively. For serotypes 1 and 2 the seroprevalence did not significantly change with age (p=0.09, p=0.44 respectively); for serotype 3 it increased with age (from 65% in 1-2 year-olds to 91.1% in 4-5-year olds; p<0.001). We did not identify any risk factors for type 2 seronegativity. Conclusions With type 2 seroprevalence close to 90%, the risk of emergence of new cVDPV2 outbreaks in Niger is low, however, the risk of cVDPV2 importations from neighbouring countries leading to local transmission persists. Niger should maintain the outbreak response readiness capacity; and further strengthen its routine immunization.

Intestinal antibody responses to two novel live attenuated type 2 oral poliovirus vaccines in healthy adults in Belgium

In a blinded phase 1 trial (EudraCT 2017-0000908-21; NCT03430349) in Belgium, healthy adults (18 to 50 years) previously immunized exclusively with inactivated polio vaccine were administered a single dose of one of two novel type 2 oral polio vaccines (nOPV2-c1: S2/cre5/S15domV/rec1/hifi3 (N=15); nOPV2-c2: S2/S15domV/CpG40 (N=15)) and isolated for 28 days in a purpose-built containment facility. Using stool samples collected near days 0, 7, 14, and 28, we evaluated intestinal neutralization and IgA responses to the novel OPV2s and found that nOPV2-c1 and nOPV2-c2 induced detectable poliovirus type 2-specific intestinal neutralizing responses in 40.0% and 46.7% of participants respectively.

Public Health Response to Restore Polio Free Status in Malaysia

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

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

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

Risk Assessment and Virological Monitoring Following an Accidental Exposure to Concentrated Sabin Poliovirus Type 3 in France, November 2018

The safe and secure containment of infectious poliovirus (PV) in facilities where live PV are handled is the condition to achieve and maintain poliomyelitis eradication. Despite precautions to minimize the risk of release of PV from such facilities to the environment, breaches of containment have already been documented. Here, we report the management of an incident that occurred on 30 November 2018 in a French vaccine manufacturing plant. Five adequately vaccinated operators were exposed to a Sabin poliovirus type 3 (PV3) spill. A microbiological risk assessment was conducted and the operators were monitored for PV shedding. On day 5 after exposure, Sabin PV3 was detected only in the stool sample of the most exposed worker. Shedding of Sabin PV3 (as detected by viral culture) was restricted to a very short period (less than 15 days). Monitoring of this incident was an opportunity to assess the relevance of our national response plan. We concluded that the measures undertaken and reported here were appropriate and proportional.

Structure of the PCBP2/stem–loop IV complex underlying translation initiation mediated by the poliovirus type I IRES

The poliovirus type I IRES is able to recruit ribosomal machinery only in the presence of host factor PCBP2 that binds to stem–loop IV of the IRES. When PCBP2 is cleaved in its linker region by viral proteinase 3CD, translation initiation ceases allowing the next stage of replication to commence. Here, we investigate the interaction of PCBP2 with the apical region of stem–loop IV (SLIVm) of poliovirus RNA in its full-length and truncated form. CryoEM structure reconstruction of the full-length PCBP2 in complex with SLIVm solved to 6.1 Å resolution reveals a compact globular complex of PCBP2 interacting with the cruciform RNA via KH domains and featuring a prominent GNRA tetraloop. SEC-SAXS, SHAPE and hydroxyl-radical cleavage establish that PCBP2 stabilizes the SLIVm structure, but upon cleavage in the linker domain the complex becomes more flexible and base accessible. Limited proteolysis and REMSA demonstrate the accessibility of the linker region in the PCBP2/SLIVm complex and consequent loss of affinity of PCBP2 for the SLIVm upon cleavage. Together this study sheds light on the structural features of the PCBP2/SLIV complex vital for ribosomal docking, and the way in which this key functional interaction is regulated following translation of the poliovirus genome.

Australian National Enterovirus Reference Laboratory annual report, 2016

Australia monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2016, no cases of poliomyelitis were reported from clinical surveillance and Australia reported 1.38 non-polio AFP cases per 100,000 children, meeting the WHO performance criterion for a sensitive surveillance system. Several non-polio enteroviruses, coxsackievirus A6, enterovirus A71, enterovirus A74 and enterovirus D68, were identified from clinical specimens collected from AFP cases. The global withdrawal of Sabin poliovirus type 2 from oral polio vaccine occurred in April 2016. This event represents the start of the polio endgame with an increased focus on the laboratory containment of all remaining wild and vaccine strains of poliovirus type 2. The National Enterovirus Reference Laboratory was designated as a polio essential facility as part of this process. In 2016, 37 cases of wild polio were reported with three countries remaining endemic: Afghanistan, Nigeria and Pakistan. Nigeria was declared polio-free in 2015, after 12 months without detection of wild poliovirus, but was reinstated as an endemic country after the reporting of four cases in August 2016. This is a salient reminder of the need to maintain sensitive surveillance for poliovirus until global eradication is certified.

Australian National Enterovirus Reference Laboratory annual report, 2015

Australia conducts surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years as recommended by the World Health Organization (WHO) as the main method to monitor its polio-free status. Cases of AFP in children are notified to the Australian Paediatric Surveillance Unit or the Paediatric Active Enhanced Disease Surveillance System and faecal specimens are referred for virological investigation to the National Enterovirus Reference Laboratory. In 2015, no cases of poliomyelitis were reported from clinical surveillance and Australia reported 1.2 non-polio AFP cases per 100,000 children, meeting the WHO performance criterion for a sensitive surveillance system. Two non-polio enteroviruses, enterovirus A71 and coxsackievirus B3, were identified from clinical specimens collected from AFP cases. Australia complements the clinical surveillance program with enterovirus and environmental surveillance for poliovirus. Two Sabin-like polioviruses were isolated from sewage collected in Melbourne in 2015, which would have been imported from a country that uses the oral polio vaccine. The global eradication of wild poliovirus type 2 was certified in 2015 and Sabin poliovirus type 2 will be withdrawn from oral polio vaccine in April 2016. Laboratory containment of all remaining wild and vaccine strains of poliovirus type 2 will occur in 2016 and the National Enterovirus Reference Laboratory was designated as a polio essential facility. Globally, in 2015, 74 cases of polio were reported, only in the two remaining countries endemic for wild poliovirus: Afghanistan and Pakistan. This is the lowest number reported since the global polio eradication program was initiated.

Wild Poliovirus Type 1 in Oman: A re-emerging threat that requires urgent, targeted and strategic preparedness

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