Viral genetics and transmission dynamics in the second wave of mpox outbreak in Portugal and forecasting public health scenarios

Abstract

In 2023, a second wave of the global mpox epidemic, which is mainly affecting men who have sex with men (MSM), was observed in some countries. Herein, we benefited from a large viral sequence sampling (76/121; 63%) and vast epidemiological data to characterise the re-emergence and circulation of the Monkeypox virus (MPXV) in Portugal during 2023. We also modelled transmission and forecasted public health scenarios through a compartmental susceptible-exposed-infectious-recovered (SEIR) model. Our results suggest that the 2023 mpox wave in Portugal resulted from limited introduction(s) of MPXV belonging to C.1.1 sublineage, hypothetically from Asia, followed by sustained viral transmission and potential exportation to other countries. We estimated that the contribution of the MSM high sexual activity group to mpox transmission was 120 (95% CrI: 30-3553) times higher than that of the low sexual activity group. However, among the high sexual activity group, vaccinated individuals likely contributed approximately eight times less [0.123 (95% CrI: 0.068-0.208)] than the unvaccinated ones. Vaccination was also linked to potential reduced disease severity, with a Mpox Severity Score of 6.0 in the vaccinated group compared to 7.0 in unvaccinated individuals. Scenario analysis indicated that transmission is highly sensitive to sexual behaviour, projecting that a slight increase in the MSM sub-population with high sexual activity can trigger new mpox waves. This study strongly supports that continued vaccination, targeted awareness among risk groups and routine genomic epidemiology is needed to anticipate and respond to novel MPXV threats (e.g. global dissemination of clade I viruses).

Keywords: MSM; Monkeypox virus; high sexual activity; second wave; vaccination.

Figure 1.

Vaccinated individuals present lower MPox Severity Score (Mpox-SS) values than unvaccinated individuals. Mpox-SS evaluation between vaccinated and unvaccinated patients using the Wilcoxon rank-sum test. Results are presented as box and whisker plots, with median and interquartile ranges represented in boxes and ranges presented as whiskers. The asterisk (*) indicates that the p-value of the statistical test is less than the significance level of 0.05.

Figure 2.

The second mpox wave in Portugal was driven by MPXV from lineage C.1.1. A. Nextstrain phylogenetic tree (branch lengths as a measure of nucleotide divergence) enrolling MPXV sequences collected in Portugal during the study period (June 14, 2023, and September 19, 2023), sequences from the 2022 outbreak in Portugal of the B.1.3 lineage, as well as publicly available international sequences from the B.1.3, C.1 and C.1.1 lineages collected within 2023 (as of December 2023). B. Time-scaled Nextstrain phylogenetic tree using the same dataset as in panel A. Asterisk (*) marks the C.1.1 sub-cluster (defined by the G152866A mutation, concerning MPXV-M5312_HM12_Rivers genome; NC_063383.1) enrolling all Portuguese sequences from the second mpox wave. Node colors represent different countries.

Figure 3.

Transmission modelling of the second mpox wave in Portugal and forecasting public health scenarios through a compartmental susceptible-exposed-infectious-recovered (SEIR) model. The model was fitted using Bayesian techniques. A (top). Describes the model fit to the observed data of weekly incident cases (as represented by the black dots). The fit is presented by the mean trajectory of the number of infections along with the 2.5% and 97.5% percentiles (95% CrI). A (bottom). Presents the median evolution of the reproduction number along with 95% CrI. The reproduction number was computed via the next generation method. B. presents the weekly-modelled incidence for the second wave along with the associated trajectories for the possible epidemic scenarios for the summer of 2024 posed in the methods section.