The Origins and Risk Factors for Serotype-2 Vaccine-Derived Poliovirus Emergences in Africa During 2016-2019.

Serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread to cause emergences of vaccine-derived poliovirus (VDPV2). After its global withdrawal from routine immunization in 2016, outbreak response use has created a cycle of VDPV2 emergences that threaten eradication. We implemented a hierarchical model based on VP1 region genetic divergence, time, and location to attribute emergences to campaigns and identify risk factors. We found that a 10 percentage point increase in population immunity in children younger than 5 years at the campaign time and location corresponds to a 18.0% decrease (95% credible interval [CrI], 6.3%-28%) in per-campaign relative risk, and that campaign size is associated with emergence risk (relative risk scaling with population size to a power of 0.80; 95% CrI, .50-1.10). Our results imply how Sabin OPV2 can be used alongside the genetically stable but supply-limited novel OPV2 (listed for emergency use in November 2020) to minimize emergence risk.

A circulating vaccine-derived poliovirus type 2 outbreak in a chronic conflict setting: a descriptive epidemiological study in South Sudan - 2020 to 2021.

BACKGROUND: In this study, we describe the epidemiological profile of an outbreak of the circulating Vaccine Derived Polio Virus type 2 in South Sudan from 2020 to 2021. METHOD: We conducted a retrospective descriptive epidemiological study using data from the national polio/AFP surveillance database, the outbreak investigation reports, and the vaccination coverage survey databases stored at the national level. RESULTS: Between September 2020 and April 2021, 59 cases of the circulating virus were confirmed in the country, with 50 cases in 2020 and 9 cases in 2021. More cases were males (56%) under five (93%). The median age of the cases was 23.4 ± 11.9 months, ranging from 1 to 84 months. All states, with 28 out of the 80 counties, reported at least one case. Most of the cases (44, 75%) were reported from five states, namely Warrap (31%), Western Bahr el Ghazal (12%), Unity (12%), Central Equatoria (10%), and Jonglei (10%). Four counties accounted for 45.8% of the cases; these are Gogrial West with 12 (20%), Jur River with 5 (8.5%), Tonj North with 5 (8.5%), and Juba with 5 (8.5%) cases. The immunization history of the confirmed cases indicated that 14 (24%) of the affected children had never received any doses of oral polio or injectable vaccines either from routine or during supplemental immunization before the onset of paralysis, 17 (28.8%) had received 1 to 2 doses, while 28 (47.5%) had received 3 or more doses (Fig. 4). Two immunization campaigns and a mop-up were conducted with monovalent Oral Polio Vaccine type 2 in response to the outbreak, with administrative coverage of 91.1%, 99.1%, and 97% for the first, second, and mop-up rounds, respectively. CONCLUSION: The emergence of the circulating vaccine-derived poliovirus outbreak in South Sudan was due to low population immunity, highlighting the need to improve the country's routine and polio immunization campaign coverage.

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique.

BACKGROUND: The monovalent type 2 oral poliovirus vaccine (mOPV2) stockpile is low. One potential strategy to stretch the existing mOPV2 supply is to administer a reduced dose: 1 drop instead of 2. METHODS: We conducted a randomized, controlled, open-label, noninferiority trial (10% margin) to compared immunogenicity after administration of 1 versus 2 drops of mOPV2. We enrolled 9-22-month-old infants from Mocuba district of Mozambique. Poliovirus neutralizing antibodies were measured in serum samples collected before and 1 month after mOPV2 administration. Immune response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) after vaccination or boosting titers by ≥4-fold for those with titers between 1:8 and 1:362 at baseline. The trial was registered at anzctr.org.au (no. ACTRN12619000184178p). RESULTS: We enrolled 378 children, and 262 (69%) completed per-protocol requirements. The immune response of mOPV2 was 53.6% (95% confidence interval, 44.9%-62.1%) and 60.6% (52.2%-68.4%) in 1-drop and 2-drop recipients, respectively. The noninferiority margin of the 10% was not reached (difference, 7.0%; 95% confidence interval, -5.0% to 19.0%). CONCLUSION: A small loss of immunogenicity of reduced mOPV2 was observed. Although the noninferiority target was not achieved, the Strategic Advisory Group of Experts on Immunization recommended the 1-drop strategy as a dose-sparing measure if mOPV2 supplies deteriorate further.

Monovalent type 2 OPV (mOPV2) management in the field: Interventions and lessons learned.

The polio endgame strategy calls for ending the use of and removal of all Sabin vaccines globally given the risks of generation and spread of cVDPVs. With the successful eradication of wild poliovirus type 2 in 2015, the process of removing type 2 Sabin vaccines began with the switch from tOPV to bOPV across national vaccination programs. Following the tOPV to bOPV switch in April/May 2016, monovalent type 2 OPV (mOPV2) has been put into use in response to detected cVDPV2 polioviruses outbreaks. Between 31 May 2016 and 30 Jun 2020, 453 million doses of mOPV2 were provided to 21 countries to conduct 235 campaigns to respond to cVDPV2 outbreaks and high-risk events. However, the use of this vaccine paradoxically reintroduces live attenuated type 2 poliovirus into the populations and the environment, therefore, poses a risk for the emergence of new VDPV2s. Thus, it is critical to carefully and appropriately manage all in-country mOPV2 stocks utilized in outbreak response to minimize this risk. In this article, we examine the performance of mOPV2 vaccine management utilized for various outbreak responses after the switch.We present the major challenges faced and the lessons learned, to improve technical guidance and future response activities. Performance varied significantly across countries in terms of each of the activity areas evaluated. There were major gaps, especially in terms of vaccine accountability, and in many instances large numbers of vials went unaccounted presenting additional risk for further VDPV2 emergences. We have shown that especially at the beginning of implementation, insufficient attention has been given to mOPV2 vaccine management. Enhanced focus on mOPV2 vaccine management in line with the lessons learned presented in this paper should be a priority for public health programs and countries to consider and adapt in future VDPV2 responses as well as potential future activities associated with eventual complete withdrawal & cessation of OPV.These experiences can also be extended to other vaccines for which strict stock management and containment measures are required.