Monkeypox: a review of epidemiological modelling studies and how modelling has led to mechanistic insight

Abstract

Human monkeypox (mpox) virus is a viral zoonosis that belongs to the Orthopoxvirus genus of the Poxviridae family, which presents with similar symptoms as those seen in human smallpox patients. Mpox is an increasing concern globally, with over 80,000 cases in non-endemic countries as of December 2022. In this review, we provide a brief history and ecology of mpox, its basic virology, and the key differences in mpox viral fitness traits before and after 2022. We summarize and critique current knowledge from epidemiological mathematical models, within-host models, and between-host transmission models using the One Health approach, where we distinguish between models that focus on immunity from vaccination, geography, climatic variables, as well as animal models. We report various epidemiological parameters, such as the reproduction number, R₀, in a condensed format to facilitate comparison between studies. We focus on how mathematical modelling studies have led to novel mechanistic insight into mpox transmission and pathogenesis. As mpox is predicted to lead to further infection peaks in many historically non-endemic countries, mathematical modelling studies of mpox can provide rapid actionable insights into viral dynamics to guide public health measures and mitigation strategies.

Keywords: MPXV; One Health; climatic variables; mathematical modelling; monkeypox; mpox; mpox vaccination; reproduction number.

Figure 1.

Cumulative mpox cases for the 2022 epidemic from 1 January 2022, through 17 November 2022. Heatmap constructed from publicly available WHO data (ref. [3], accessed 17 November 2022).

Figure 2.

Cumulative mpox cases for the 2022 epidemic from 1 January 2022 through 17 November 2022, normalized by country total population. Heatmap constructed from publicly available WHO data (ref. [3], accessed 17 November 2022). Country population data accessed from WolframAlpha Knowledgebase on 29 November 2022.

Figure 3.

Costs versus vaccination rate with a high rate of the effective human-to-human transmission (β_hh = 60). (a) Fully endemic equilibrium and (b) Semi-endemic equilibrium. Reprinted by permission from PeerJ from ref. [55]. Copyright 2020.

Figure 4.

(a) Schematic of basic SIR model with standard incidence, similar as used to model mpox dynamics for the 2022 pandemic [50, 59]. (b) Global reported mpox cases as a function of weeks for the year 2022. Data accessed from publicly available WHO data (ref. [3], accessed 17 November2022).

Figure 5.

(a) Visualization of the relationship between smallpox vaccination and cross-immunity conferred to mpox virus rates at a population (blue) and individual level (red) in Nigeria from 1970 to 2018. Reprinted by permission from Centers for Disease Control and Prevention from ref. [42]. Copyright 2021. (b) Predicted change of the reproduction number R for MPX as a function of immunity in a population to orthopoxvirus species (provided by smallpox vaccine). Blue circles show a scenario where the vaccination percentage is high, most of the population presents high-level cross-immunity against orthopoxvirus species, and the mpox R value is low. Yellow circles show the scenario where vaccination and cross-immunity rates are low, and mpox R-value increases to >2.5. Reprinted by permission from the World Health Organization from ref. [56]. Copyright 2020.

Figure 6.

(a) Two-dimensional representation (annual mean temperature and annual mean precipitation) of ecological niche models developed for two mpox reservoir species cricetomys gambianus (white diamonds) and cricetomys emini (grey diamonds) across tropical sub-Saharan Africa. Reprinted by permission from Oxford University Press from ref. [118]. Copyright 2006. (b) Observed and predicted human mpox occurrence under present and future climate conditions with reservoir species as predictor variables in Central and Western Africa. The average projected change in occurrence probability for eight climate change scenarios for 2050 (middle) and 2080 (bottom). Reprinted and modified by permission from PLOS One from ref. [119]. Copyright 2013. (c) mpox prevalence detected in dried museum specimens of potential mpox reservoir species, with an underlying layer representing tree cover, with darker greens corresponding to high cover percentages. Reprinted by permission from The Royal Society Publishing from ref. [120]. Copyright 2018.