The Fading of the Mpox Outbreak Among Men Who Have Sex With Men: A Mathematical Modelling Study

BACKGROUND: In the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioural adaptations. METHODS: We developed a transmission model and accounted for possible behavioural adaptations: less casual partners and shorter time until MSM with mpox refrain from sexual contacts. RESULTS: Without behavioural adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioural adaptations in the model, we found a decline of 16-18% in numbers of casual partners in June and 13-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination. CONCLUSIONS: The limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioural adaptations. Immunity among those most sexually active is essential to impede mpox resurgence

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline with less than 1% of sexually active MSM population infected regardless of interventions or behavioural changes. Consistently, we found that many countries and US states experienced an epidemic peak with cumulative cases of around 0.1-0.5% of MSM population. The observed decline in cases may not necessarily be attributable to interventions or behavioural changes primarily

Estimated incubation period distributions of mpox using cases from two international European festivals and outbreaks in a club in Berlin, May to June 2022

Background Since May 2022, an mpox outbreak affecting primarily men who have sex with men (MSM) has occurred in numerous non-endemic countries worldwide. As MSM frequently reported multiple sexual encounters in this outbreak, reliably determining the time of infection is difficult; consequently, estimation of the incubation period is challenging. Aim We aimed to provide valid and precise estimates of the incubation period distribution of mpox by using cases associated with early outbreak settings where infection likely occurred. Methods Colleagues in European countries were invited to provide information on exposure intervals and date of symptom onset for mpox cases who attended a fetish festival in Antwerp, Belgium, a gay pride festival in Gran Canaria, Spain or a particular club in Berlin, Germany, where early mpox outbreaks occurred. Cases of these outbreaks were pooled; doubly censored models using the log-normal, Weibull and Gamma distributions were fitted to estimate the incubation period distribution. Results We included data on 122 laboratory-confirmed cases from 10 European countries. Depending on the distribution used, the median incubation period ranged between 8 and 9 days, with 5th and 95th percentiles ranging from 2 to 3 and from 20 to 23 days, respectively. The shortest interval that included 50% of incubation periods spanned 8 days (4–11 days). Conclusion Current public health management of close contacts should consider that in approximately 5% of cases, the incubation period exceeds the commonly used monitoring period of 21 days

Wastewater-based reproduction numbers and projections of COVID-19 cases in three areas in Japan, November 2021 to December 2022

Background: Wastewater surveillance has expanded globally as a means to monitor spread of infectious diseases. An inherent challenge is substantial noise and bias in wastewater data because of the sampling and quantification process, limiting the applicability of wastewater surveillance as a monitoring tool. Aim: To present an analytical framework for capturing the growth trend of circulating infections from wastewater data and conducting scenario analyses to guide policy decisions. Methods: We developed a mathematical model for translating the observed SARS-CoV-2 viral load in wastewater into effective reproduction numbers. We used an extended Kalman filter to infer underlying transmissions by smoothing out observational noise. We also illustrated the impact of different countermeasures such as expanded vaccinations and non-pharmaceutical interventions on the projected number of cases using three study areas in Japan during 2021–22 as an example. Results: Observed notified cases were matched with the range of cases estimated by our approach with wastewater data only, across different study areas and virus quantification methods, especially when the disease prevalence was high. Estimated reproduction numbers derived from wastewater data were consistent with notification-based reproduction numbers. Our projections showed that a 10–20% increase in vaccination coverage or a 10% reduction in contact rate may suffice to initiate a declining trend in study areas. Conclusion: Our study demonstrates how wastewater data can be used to track reproduction numbers and perform scenario modelling to inform policy decisions. The proposed framework complements conventional clinical surveillance, especially when reliable and timely epidemiological data are not available

Accumulation of immunity in heavy-tailed sexual contact networks shapes mpox outbreak sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline with less than 1% of sexually active MSM population infected regardless of interventions or behavioural changes. Consistently, we found that many countries and US states experienced an epidemic peak with cumulative cases of around 0.1-0.5% of MSM population. The observed decline in cases may not necessarily be attributable to interventions or behavioural changes primarily

Modelling the effectiveness of an isolation strategy for managing mpox outbreaks with variable infectiousness profiles

The global outbreak of mpox in 2022 and subsequent sporadic outbreaks in 2023 highlighted the importance of nonpharmaceutical interventions such as case isolation. Individual variations in viral shedding dynamics may lead to either premature ending of isolation for infectious individuals, or unnecessarily prolonged isolation for those who are no longer infectious. Here, we developed a modeling framework to characterize heterogeneous mpox infectiousness profiles – specifically, when infected individuals cease to be infectious – based on viral load data. We examined the potential effectiveness of three different isolation rules: a symptom-based rule (the current guideline in many countries) and rules permitting individuals to stop isolating after either a fixed duration or following tests that indicate that they are no longer likely to be infectious. Our analysis suggests that the duration of viral shedding ranges from 23 to 50 days between individuals. The risk of infected individuals ending isolation too early was estimated to be 8.8% (95% CI: 6.7–10.5) after symptom clearance and 5.4% (95% CI: 4.1–6.7) after 3 weeks of isolation. While these results suggest that the current standard practice for ending isolation is effective, we found that unnecessary isolation following the infectious period could be reduced by adopting a testing-based rule

Patterns of SARS-CoV-2 circulation revealed by a nationwide sewage surveillance programme, the Netherlands, August 2020 to February 2022

BackgroundSurveillance of SARS-CoV-2 in wastewater offers a near real-time tool to track circulation of SARS-CoV-2 at a local scale. However, individual measurements of SARS-CoV-2 in sewage are noisy, inherently variable and can be left-censored.AimWe aimed to infer latent virus loads in a comprehensive sewage surveillance programme that includes all sewage treatment plants (STPs) in the Netherlands and covers 99.6% of the Dutch population.MethodsWe applied a multilevel Bayesian penalised spline model to estimate time- and STP-specific virus loads based on water flow-adjusted SARS-CoV-2 qRT-PCR data for one to four sewage samples per week for each of the more than 300 STPs.ResultsThe model captured the epidemic upsurges and downturns in the Netherlands, despite substantial day-to-day variation in the measurements. Estimated STP virus loads varied by more than two orders of magnitude, from ca 1012 virus particles per 100,000 persons per day in the epidemic trough in August 2020 to almost 1015 per 100,000 in many STPs in January 2022. The timing of epidemics at the local level was slightly shifted between STPs and municipalities, which resulted in less pronounced peaks and troughs at the national level.ConclusionAlthough substantial day-to-day variation is observed in virus load measurements, wastewater-based surveillance of SARS-CoV-2 that is performed at high sampling frequency can track long-term progression of an epidemic at a local scale in near real time

The transmissibility of noroviruses : Statistical modeling of outbreak events with known route of transmission in Japan

In Japan, the fraction of norovirus outbreaks attributable to human-to-human transmission has increased with time, and the timing of the increased fraction has coincided with the increase in the observed fraction of genogroup II genotype 4 (GII.4). The present study aimed to estimate the time-dependent changes in the transmissibility of noroviruses. The effective reproduction number (Ry), for year y, was estimated by analyzing the time series surveillance data for outbreak events from 2000 to 2016. Ry was estimated by using the fraction of outbreak events that were attributable to human-to-human transmission and by employing three different statistical models that are considered to mechanistically capture the possible data-generating process in different ways. The Ry estimates ranged from 0.14 to 4.15 in value, revealing an overall increasing trend (p<0.05 for all three models). The proportion of outbreaks caused by GII and GII.4 viruses among the total events also increased with time, and positive correlations were identified between transmissibility and these proportions. Parametric modeling of Ry indicated that the time-dependent patterns of Ry were better described by a step function plus linear trend rather than the step function alone that reflects the widespread use of reverse transcriptase PCR (RT-PCR) in and after 2007 for laboratory diagnosis. Accordingly, we conclude that norovirus transmissibility has increased over the past 16 years in Japan. The change is at least partially explained by the time-dependent domination of the contagious GII genogroup (e.g., GII.4), indicating that noroviruses better fitted to humans have selectively caused the human-to-human transmissions, thereby altering the epidemiology of this pathogen

Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan

Background: Foodborne norovirus outbreak data in Japan from 2005–2006, involving virological surveillance of all symptomatic and asymptomatic individuals, were reanalyzed to estimate the asymptomatic ratio of norovirus infection along with the risk of infection and the probability of virus shedding. Methods: Employing a statistical model that is considered to capture the data-generating process of the outbreak and virus surveillance, maximum likelihood estimation of the asymptomatic ratio was implemented. Results: Assuming that all norovirus outbreaks (n = 55) were the result of random sampling from an identical distribution and ignoring genogroup and genotype specificities, the asymptomatic ratio was estimated at 32.1% (95% confidence interval [CI], 27.7–36.7). Although not significant, separate estimation of the asymptomatic ratio of the GII.4 genotype appeared to be greater than other genotypes and was estimated at 40.7% (95% CI, 32.8–49.0). Conclusion: The present study offered the first explicit empirical estimates of the asymptomatic ratio of norovirus infection in natural infection settings. The estimate of about 30% was consistent with those derived from volunteer challenge studies. Practical difficulty in controlling GII.4 outbreaks was supported by the data, considering that a large estimate of the asymptomatic ratio was obtained for the GII.4 genotype