Megan Auzenbergs

The 2021 importation of wild poliovirus serotype 1 (WPV1) into Malawi with subsequent international spread represented the first WPV1 cases in Africa since 2016. Preventing importations and spread of WPV1 is critical and dependent on population immunity provided through routine immunisation (RI) and supplementary immunisation activities (SIAs). We aim to estimate outbreak risk and costs, given the importation of WPV1 for non-endemic countries in the WHO Africa region. We developed a stochastic mathematical model of polio transmission dynamics to evaluate the probability of an outbreak, expected number of poliomyelitis cases, costs and incremental cost-effectiveness ratios under different vaccination strategies. Across variable RI coverage, we explore three key strategies: RI+outbreak SIAs (oSIAs), RI+oSIAs+annual preventative SIAs (pSIAs) and RI+oSIAs+biennial pSIAs. Results are presented in 2023 USD over a 5year- time horizon from the Global Polio Eradication Initiative (GPEI) and health system perspectives. The annual pSIA strategy has the greatest probability of no outbreaks in comparison to other strategies: under our model assumptions, annual pSIAs result in an 80% probability of no outbreaks when RI coverage is ≥50%. The biennial pSIA strategy requires RI coverage ≥65% to achieve an equivalent risk of no outbreaks. The strategy with no pSIAs requires ≥75% RI coverage to achieve an equivalent risk of no outbreaks. For the health system, when RI coverage is between 35% and 60%, both pSIA strategies are cost-saving. For the GPEI, below 65% RI pSIA strategies are cost-effective, but the biennial pSIA strategy incurs higher costs in comparison to annual pSIAs due to more oSIAs required to stop outbreaks. Prioritisation of pSIAs must balance outbreak risk against implementation costs, ideally favouring the smallest manageable outbreak risk compatible with elimination. We infer that there are few short-term risks due to population immunity from RI, but without pSIAs, long-term risks accumulate and can result in outbreaks with the potential for international spread.

A fundamental question in the global commitment to polio eradication is how long a period of absence would be consistent with regional elimination, and the safe withdrawal of the oral polio vaccine is contingent on the answer. We present a statistical framework to model the time-varying sensitivity of two key components of polio surveillance - environmental sampling and clinical cases of acute flaccid paralysis - for detecting infection on a monthly basis at the local government authority level. We use this to estimate the probability of freedom from infection (FFI) at a critical prevalence level that is consistent with interruption of transmission, given the absence of virus in collected samples. We validated this framework against two periods of poliovirus absence in Nigeria (2014-2016 and 2016-2020). Our model highlights substantial heterogeneity in surveillance sensitivity over time and space and, given this, concluded an 85% probability (95% uncertainty interval: 77.1-90.2%) of the country being free from WPV1 infection after 23 months without detection from July 2014. Detection of WPV1 in July 2016 demonstrated that circulation had indeed persisted during this time. In contrast, we conclude a probability of 98% (97.9-98.7%) by the time elimination of the serotype was officially declared in 2020. The inferred probability of FFI during both time periods was found to be consistent with the retrospectively known status of regional elimination. This supports the validity of applying this framework prospectively to inform the certification of wild poliovirus elimination from remaining endemic regions, and to determine the resolution of cVDPV2 outbreaks.

Chikungunya can have longstanding effects on health and quality of life. Alongside the recent approval of the world’s first chikungunya vaccine by the US Food and Drug Administration in November 2023 and with new chikungunya vaccines in the pipeline, it is important to understand the perspectives of stakeholders before vaccine rollout. Our study aim is to identify key programmatic considerations and gaps in Evidence-to-Recommendation criteria for chikungunya vaccine introduction. We used purposive and snowball sampling to identify global, national, and subnational stakeholders from outbreak prone areas, including Latin America, Asia, and Africa. Semi-structured in-depth interviews were conducted and analysed using qualitative descriptive methods. We found that perspectives varied between tiers of stakeholders and geographies. Unknown disease burden, diagnostics, non-specific disease surveillance, undefined target populations for vaccination, and low disease prioritisation were critical challenges identified by stakeholders that need to be addressed to facilitate rolling out a chikungunya vaccine. Future investments should address these challenges to generate useful evidence for decision-making on new chikungunya vaccine introduction.

Chikungunya can have longstanding effects on health and quality of life. Alongside the licensing of new chikungunya vaccines in the pipeline, it is important to understand the perspectives of stakeholders before vaccine rollout. Our study aim is to identify key programmatic considerations for chikungunya vaccine introduction in countries at risk of chikungunya outbreaks. We used purposive and snowball sampling to identify global, national, and subnational stakeholders from outbreak prone areas, including Latin America, Asia, and Africa. Semi-structured in-depth interviews were conducted and analysed using qualitative descriptive methods. We found that perspectives varied between tiers of stakeholders and geographies. Unknown disease burden, diagnostics, non-specific disease surveillance, undefined target populations for vaccination, and low disease prioritisation were critical challenges identified by stakeholders that need to be addressed to facilitate rolling out a chikungunya vaccine. Future investments should address these challenges to generate useful evidence for decision-making on new chikungunya vaccine introduction.

Background Polio eradication was threatened in 2022 by importation of wild poliovirus serotype 1 into Malawi with subsequent international spread, representing the first wild polio cases in Africa since 2014. Preventing importations and spread of wild poliovirus is critical, and dependent on population immunity provided through routine immunisation and supplementary immunisation activities (SIAs). However, the scale of preventative SIAs has reduced in recent years due to financial constraints. Methods We developed a mathematical model of polio transmission dynamics to evaluate the probability of an outbreak, expected number of poliomyelitis cases, and the costs associated with vaccination delivery through routine immunisation (RI), outbreak response SIAs (oSIAs) and preventative SIAs (pSIAs). Across varying levels of routine immunisation coverage, we explore three key strategies: RI+oSIAs, RI+oSIAs+annual pSIAs, and RI+oSIAs+biannual pSIAs. Results The annual pSIA strategy (RI+oSIAs+annual pSIAs) had higher costs but greater probability of no outbreaks: under our model assumptions, annual pSIAs result in 80% probability of no outbreaks when routine immunisation coverage ≥50%. The biannual pSIA strategy (RI+oSIAs+biannual pSIAs) costs less and averts more outbreaks than RI+oSIAs, but RI coverage ≥65% was required to achieve equivalent risk of no outbreaks. The strategy with no pSIAs (RI+oSIAs) had the lowest costs but required ≥75% RI coverage to achieve equivalent risk of no outbreaks. Conclusion Prioritisation of pSIAs must balance outbreak risk against implementation costs, ideally favouring the smallest manageable outbreak risk compatible with elimination. We infer that there are few short-term risks due to population immunity from RI, but without pSIAs, long-term risks accumulate and can result in outbreaks with potential for international spread. We do not consider the costs of further delaying the eradication timeline or societal implications of outbreaks, both of which emphasise the need for pSIAs.

Background: Circulating vaccine derived poliovirus (cVDPV) outbreaks remain a threat to polio eradication. To reduce cases of polio from cVDPV of serotype 2, the serotype 2 component of the vaccine has been removed from the global vaccine supply, but outbreaks of cVDPV2 have continued. The objective of this work is to understand the factors associated with later detection in order to improve detection of these unwanted events. Methods: The number of nucleotide differences between each cVDPV outbreak and the oral polio vaccine (OPV) strain was used to approximate the time from emergence to detection. Only independent emergences were included in the analysis. Variables such as serotype, surveillance quality, and World Health Organization (WHO) region were tested in a negative binomial regression model to ascertain whether these variables were associated with higher nucleotide differences upon detection. Results: In total, 74 outbreaks were analysed from 24 countries between 2004-2019. For serotype 1 (n=10), the median time from seeding until outbreak detection was 572 (95% uncertainty interval (UI) 279-2016), for serotype 2 (n=59), 276 (95% UI 172-765) days, and for serotype 3 (n=5), 472 (95% UI 392-603) days. Significant improvement in the time to detection was found with increasing surveillance of non-polio acute flaccid paralysis (AFP) and adequate stool collection. Conclusions: cVDPVs remain a risk; all WHO regions have reported at least one VDPV outbreak since the first outbreak in 2000 and outbreak response campaigns using monovalent OPV type 2 risk seeding future outbreaks. Maintaining surveillance for poliomyelitis after local elimination is essential to quickly respond to both emergence of VDPVs and potential importations as low-quality AFP surveillance causes outbreaks to continue undetected. Considerable variation in the time between emergence and detection of VDPVs were apparent, and other than surveillance quality and inclusion of environmental surveillance, the reasons for this remain unclear.

Background WHO recommends ≥95% population coverage with two doses of measles-containing vaccine (MCV). Most countries used routine services to offer MCV1 and later, MCV2. Many countries conducted supplementary immunisation activities (SIAs), offering vaccination to all persons in a given age range irrespective of prior vaccination history. We estimated the relative impact of each dose and delivery route in 14 high burden countries. Methods We used an age-structured dynamic model (DynaMICE), to estimate the health impact of different vaccination strategies on measles susceptibility and burden over 2000-2020. We estimated their incremental impact using averted cases and deaths and their efficiency using number needed to vaccinate (NNV) to avert an additional measles case. Findings Compared to no vaccination, MCV1 implementation averted 823 million cases and 9.5 million deaths, with a median NNV of 1.41. Adding routine MCV2 to MCV1 further averted 108 million cases and 0.4 million deaths, while adding SIAs to MCV1 led to 249 million averted cases and 4 million deaths. Despite a larger incremental impact, adding SIAs to MCV1 showed reduced efficiency compared to adding routine MCV2, with median NNVs of 6.15 and 5.41, respectively. Interpretation Vaccination strategies including non-selective SIAs reach a greater proportion of unvaccinated children and reduce burden more than MCV2 alone, but efficiency is somewhat lower because of the wide age groups included in SIAs. This analysis provides insight to improve health impact and efficiency of measles vaccination. Funding Gavi, the Vaccine Alliance, and the Bill & Melinda Gates Foundation (OPP1157270)

Background: Circulating vaccine derived poliovirus (cVDPV) outbreaks remain a threat to polio eradication. To reduce cases of polio from cVDPV of serotype 2, the serotype 2 component of the vaccine has been removed from the global vaccine supply, but outbreaks of cVDPV2 have continued. The objective of this work is to understand the factors associated with later detection in order to improve detection of these unwanted events. Methods: The number of nucleotide differences between each cVDPV outbreak and the oral polio vaccine (OPV) strain was used to approximate the time from emergence to detection. Only independent emergences were included in the analysis. Variables such as serotype, surveillance quality, and World Health Organization (WHO) region were tested in a negative binomial regression model to ascertain whether these variables were associated with higher nucleotide differences upon detection. Results: In total, 74 outbreaks were analysed from 24 countries between 2004-2019. For serotype 1 (n=10), the median time from seeding until outbreak detection was 284 (95% uncertainty interval (UI) 284-2008) days, for serotype 2 (n=59), 276 (95% UI 172-765) days, and for serotype 3 (n=5), 472 (95% UI 392-603) days. Significant improvement in the time to detection was found with increasing surveillance of non-polio acute flaccid paralysis (AFP) and adequate stool collection. Conclusions: cVDPVs remain a risk; all WHO regions have reported at least one VDPV outbreak since the first outbreak in 2000 and outbreak response campaigns using monovalent OPV type 2 risk seeding future outbreaks. Maintaining surveillance for poliomyelitis after local elimination is essential to quickly respond to both emergence of VDPVs and potential importations as low-quality AFP surveillance causes outbreaks to continue undetected. Considerable variation in the time between emergence and detection of VDPVs were apparent, and other than surveillance quality and inclusion of environmental surveillance, the reasons for this remain unclear.