Responsive modelling of the mpox epidemic in England as a cross-government and academia collaboration: the process, challenges, and lessons learned

Panovska‐Griffiths, Jasmina; Watkins, Nicholas A.; Cumming, Fergus; Hounsome, Luke; Charlett, André; Zhang, Xu‐Sheng; Finnie, Thomas; Ward, Thomas; Chand, Meera; Hutchinson, Johanna

doi:10.1016/s2666-5247(23)00151-9

Cited by 7 publications

(8 citation statements)

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“…The outbreak in the Netherlands started between the middle of April and the middle of May 2022. After May 23 rd , we assumed that awareness increased during the outbreak, resulting in a reduced time between symptom onset and diagnosis in health care, and a reduction in new sexual partners by up to 50% (27, 28). Individuals that recovered from mpox are assumed to not be infectious to others.…”

Section: Methodsmentioning

confidence: 99%

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

Shamier,

Zaeck,

Götz

et al. 2023

Preprint

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SummaryBackgroundIn the wake of the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks. Here, we combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate the risk of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM visiting the Centres for Sexual Health (CSH) in Rotterdam or Amsterdam after the introduction of vaccination and the peak of the Dutch mpox outbreak. For MSM visiting the CSH in Rotterdam, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)- specific IgG; plaque reduction neutralization tests (PRNT) were performed on a selection of samples. These observations were combined with literature data on infection dynamics and vaccine effectiveness to inform a stochastic transmission model to estimate the risk on future mpox outbreaks.FindingsThe seroprevalence of VACV-specific IgG was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Based on the correlation between serological parameters, we identified confirmed MPXV infections and inferred nine undiagnosed infections in individuals without childhood smallpox vaccination in the Rotterdam cohort (5.1%). Transmission modelling showed that the overall number of mpox cases in new outbreaks would be low, but that the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis will be a key component of any strategy to prevent new outbreaks.InterpretationOur findings indicate a reduced likelihood of future mpox outbreaks among MSM in the Netherlands under the current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities, and disease awareness.FundingNational Institute for Public Health and the Environment (RIVM), HORIZON-HLTH-2022-MPX-14 (101115188).Research in contextEvidence before this studyWe searched PubMed from database inception to July 24th, 2023, using the search terms (“monkeypox” OR “mpox” OR “orthopoxvirus”) AND (“immunity” OR “antibodies” OR vaccin*) OR (model*) OR (“epidemiology” OR “outbreak”) OR (“seroprevalence” OR “serosurveillance”), with no date or language restrictions. We included the cited references of retrieved publications in our search. We found that there are crucial knowledge gaps with respect to monkeypox virus (MPXV)-specific immunity and the impact of risk group vaccination with third-generation smallpox vaccines on the prevention of future outbreaks. No seroprevalence studies following the 2022-2023 mpox outbreak have been published yet. Recent observational studies from Israel, the United Kingdom, and the United States reported adjusted vaccine effectiveness levels between 36% - 86% following one or two doses of MVA. After the massive 2022-2023 outbreak, the number of new cases is now at a very low level, although there are continouing reports of small clusters of infections, including breakthrough infections and re-infections. This long tail to the epi curve, raises concerns about the potential of future outbreaks. We found no studies that predicted the risk of future mpox outbreaks after risk group vaccination based on measured seroprevalence data.Added value of this studyThe primary goal of this study was to estimate the risk of future mpox outbreaks among men who have sex with men (MSM) in the Netherlands using mathematical modelling based on real-world data. To this end, we used a combination of serological assays to determine the presence and abundance of (functional) poxvirus-specific antibodies in a Dutch MSM cohort. Next, we demonstrate the impact of rapid diagnosis (followed by isolation) of mpox cases on the size and duration of future outbreaks employing a mathematical model.Implications of all the available evidenceA seroprevalence level of approximately 45% among MSM in the Netherlands visiting the Centres for Sexual Health was found. Modelling showed that this seroprevalence level alone may not be sufficient to prevent future outbreaks, which emphasises the importance of continued disease awareness, and maintaining population immunity and diagnostic capacities. These insights have important implications for public health policy making and fill critical knowledge gaps to help inform surveillance activities and guide vaccination strategies.

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Section: Methodsmentioning

confidence: 99%

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

Shamier,

Zaeck,

Götz

et al. 2023

Preprint

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“…where ‫ݑ‬ ఈ,௧ is the upper bound of the 95% PI interval at time ‫,ݐ‬ ݈ ఈ,௧ is the lower bound at time t, ‫ݕ‬ ௧ is the observed mpox case incidence at ‫,ݐ‬ and ߙ ൌ 0.05 as we are working with 95% PI intervals. We then calculated the skill scores (22) for average Winkler scores, where scores are averaged across all forecasting periods, for each model, location, and forecasting horizon.…”

Section: Skill Scores and Winkler Scorementioning

confidence: 99%

“…For any emerging pathogen that rapidly transmits throughout a population, short-term forecasts of the epidemic's trajectory at different spatial scales can help guide policy and intervention strategies [8,[19][20][21][22]. However, there is little opportunity to assess forecasting performance and improve models amid an ongoing public health crisis.…”

Section: Introductionmentioning

confidence: 99%

Retrospective evaluation of short-term forecast performance of ensemble sub-epidemic frameworks and other time-series models: The 2022-2023 mpox outbreak across multiple geographical scales, July 14^th, 2022, through February 26th, 2023

Bleichrodt

Luo

Kirpich

et al. 2023

Preprint

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In May 2022, public health officials noted an unprecedented surge in Mpox cases in non-endemic countries worldwide. As the epidemic accelerated, multi-model forecasts of the epidemic's trajectory were critical in guiding the implementation of public health interventions, and in determining policy. As the case levels have significantly decreased as of mid-August, evaluating model performance is essential to advance the growing field of epidemic forecasting. Using laboratory-confirmed Mpox case data from the CDC and OWID teams through the week of January 26th, 2023, we generated retrospective sequential weekly forecasts (e.g., 1-week, 2-week, 3-week, and 4-week) for Brazil, Canada, England, France, Germany, Spain, the USA, and at the global scale using models that require minimal input data including the auto-regressive integrated moving average (ARIMA), general additive model (GAM), simple linear regression (SLR) as well as the spatial-wave and n-sub-epidemic modeling frameworks. Forecast performance was assessed using MSE, MAE, WIS, 95% PI coverage metrics as well as skill scores. Overall, the spatial-wave sub-epidemic modeling framework outcompeted other models across most locations and forecasting horizons in terms of the average MSE, MAE, and WIS. It was followed closely in success by the n-sub-epidemic top-ranked and weighted ensemble (2) models. Regarding average 95% PI coverage, the n-sub-epidemic unweighted (equally weighted top-models) ensemble (2) model performed best across all forecasting horizons for most locations. However, many locations had multiple models performing equally well in terms of the average 95% PI coverage. Both the n-sub-epidemic and spatial-wave frameworks improved considerably in average MSE, MAE, and WIS, and minimally (<10%) in average 95% PI coverage relative to the ARIMA model. Findings lend further support to sub-epidemic models for short-term forecasting epidemics of emerging and re-emerging infectious diseases.

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“…4,8 In May 2022, the UK Health Security Agency reported hMPXV in a traveler returning from Nigeria followed by several cases without travel history to known endemic countries. 8,9 Within several weeks, hMPXV infections were detected in 111 countries, including 104 non-enzootic countries leading to declaration of a Public Health Emergency of International Concern by the World Health Organization on July 23, 2022. As of August 2023, more than 89,500 cases have been reported globally.…”

Section: Introductionmentioning

confidence: 99%

“…Since 2018, there have been reports of a few travel‐associated mpox cases in the United States of America, the United Kingdom, Singapore and Israel after travel to Nigeria 4,8 . In May 2022, the UK Health Security Agency reported hMPXV in a traveler returning from Nigeria followed by several cases without travel history to known endemic countries 8,9 . Within several weeks, hMPXV infections were detected in 111 countries, including 104 non‐enzootic countries leading to declaration of a Public Health Emergency of International Concern by the World Health Organization on July 23, 2022.…”

Section: Introductionmentioning

confidence: 99%

Circulation, viral diversity and genomic rearrangement in mpox virus in the Netherlands during the 2022 outbreak and beyond

Schuele,

Boter,

Nieuwenhuijse

et al. 2024

Journal of Medical Virology

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Mpox is an emerging zoonotic disease which has now spread to over 113 countries as of August 2023, with over 89,500 confirmed human cases. The Netherlands had one of the highest incidence rates in Europe during the peak of the outbreak. In this study, we generated 158 near‐complete mpox virus (MPXV) genomes (12.4% of nationwide cases) that were collected throughout the Netherlands from the start of the outbreak in May 2022 to August 2023 to track viral evolution and investigate outbreak dynamics. We detected 14 different viral lineages, suggesting multiple introductions followed by rapid initial spread within the country. The estimated evolutionary rate was relatively high compared to previously described in orthopoxvirus literature, with an estimated 11.58 mutations per year. Genomic rearrangement events occurred at a rate of 0.63% and featured a large deletion event. In addition, based on phylogenetics, we identified multiple potential transmission clusters which could be supported by direct source‐ and contact tracing data. This led to the identification of at least two main transmission locations at the beginning of the outbreak. We conclude that whole genome sequencing of MPXV is essential to enhance our understanding of outbreak dynamics and evolution of a relatively understudied and emerging zoonotic pathogen.

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Responsive modelling of the mpox epidemic in England as a cross-government and academia collaboration: the process, challenges, and lessons learned

Cited by 7 publications

References 4 publications

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

Retrospective evaluation of short-term forecast performance of ensemble sub-epidemic frameworks and other time-series models: The 2022-2023 mpox outbreak across multiple geographical scales, July 14^th, 2022, through February 26th, 2023

Circulation, viral diversity and genomic rearrangement in mpox virus in the Netherlands during the 2022 outbreak and beyond

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Responsive modelling of the mpox epidemic in England as a cross-government and academia collaboration: the process, challenges, and lessons learned

Cited by 7 publications

References 4 publications

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

The risk of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data

Retrospective evaluation of short-term forecast performance of ensemble sub-epidemic frameworks and other time-series models: The 2022-2023 mpox outbreak across multiple geographical scales, July 14th, 2022, through February 26th, 2023

Circulation, viral diversity and genomic rearrangement in mpox virus in the Netherlands during the 2022 outbreak and beyond

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Retrospective evaluation of short-term forecast performance of ensemble sub-epidemic frameworks and other time-series models: The 2022-2023 mpox outbreak across multiple geographical scales, July 14^th, 2022, through February 26th, 2023