Written by丨ChromosomesMonkeypox is a viral zoonotic disease caused by the MPXV virus, which is predominantly endemic in West and Central Africa。Prior to 2022, cases of monkeypox outside endemic areas were mostly linked to a history of travel to Nigeria or exposure to live animals in endemic areas. On 7 May 2022, the UK first confirmed a case of monkeypox who had travelled to Nigeria. Since then, there has been a steady stream of cases of travel to endemic areas and human-to-human transmission around the world. As of July 19, 2023, a total of 88,549 cases of monkeypox have been reported globally。The epidemic is dominated by men who have sex with men (MSM), and the disease is relatively mild. On 23 July 2022, WHO declared monkeypox an international public health emergency, advocating for the investigation of the spread of the outbreak, the use of vaccines to control transmission, and guidelines for international travel。To date, it is unclear how much international travel contributes to the extent of transmission of monkeypox outbreaks in various regions, and whether national vaccination campaigns can fully contain the outbreak. February 29, 2024, from the Department of Epidemiology, University of Washington, USAmiguel i. paredesThe team is incellThe journal is published in:underdetected dispersal and extensive local transmission drove the 2022 mpox epidemic(Occult transmission and large-scale local spread fueled the monkeypox outbreak in 2022). Research analysis shows that the 2022 monkeypox outbreak is characterized by insidious, rapid local transmission among high-risk groups. Local behavioural changes have played a more important role in containing transmission than travel restrictions and vaccination campaigns. 
Genomic epidemiology is uniquely positioned to explore global and regional transmission dynamics by combining viral genomic information and epidemiological metadata to enhance public health surveillance。Current studies do not provide sufficient understanding of the extent of monkeypox transmission and the effectiveness of interventions. Here, the researchers analyzed MPXV genomic data from five regions of the world by building biogeographic and evolutionary dynamics models, combined with air traffic and epidemiological data, to reveal the characteristics of the virus in terms of community transmission, changes in case reports, and transmission heterogeneity. The study found that the importation of the virus in the early days of the outbreak contributed limited to transmission, and the travel ban had a limited effect. In the United States, monkeypox transmission declined after more than 10% of high-risk people were vaccinated. The findings highlight the importance of early routine sample screening, surveillance, and integration of genomic and epidemiological information in outbreak control. Characteristics of the spread of monkeypox outbreaksFollowing the first detection of monkeypox cases in the UK on 7 May 2022, the number of reported cases worldwide has grown rapidly. The early outbreak occurred mainly in western and southern Europe, and then spread to central Europe, forming a peak(Figure 1a).。Cases have followed in North and South America, and North America has become the region with the highest number of reported cases worldwide. The results of the global epidemic of monkeypox using a systematic geography method show that the monkeypox virus originated in Western Europe, and the virus spread process showed obvious population characteristics, and a single import from one area usually led to large-scale local transmission. The rapid spread in Western Europe has led to the importation of large quantities of the virus into the rest of the globe, with North America having the longest duration of the virus(Figure 1b).。Using an approximate structured clustering model (MASCOT) and a generalized linear model (GLM), combined with genomic and epidemiological data, the researchers extrapolated the effective population size and migration rates in different regions. Studies have found strong evidence of viral prevalence in early cases prior to initial testing, especially in the early months of the outbreak. By comparing the differences in data estimates, the study revealed evidence that cases were not tested and found that the virus spread earlier than public health surveillance before the imported cases. In addition, the study also found that clusters of outbreaks after imported cases were easier to contain. The analysis also took into account the uncertainty of case reporting and modelled significant underdetection of cases in the early stages of the outbreak. Studies of viral transmission chains have found that most virus imports result in only a single imported case, but a small number result in explosive and widespread local transmission. Early imported cases result in larger and longer-lasting chains of transmission, while importation after public health testing results in smaller outbreaks that resolve more quickly(Figure 1c).。The study also found that air passenger traffic between different regions is an important factor driving the international spread of the virus. In addition, virus importation played a smaller role in regional epidemics, causing an average of 15%-15% of new cases. After the onset of the virus epidemic, local transmission began to dominate, and the role of virus importation in the later stages of transmission was very limited. 
Figure 1Transmission characteristics of monkeypox outbreaks and vaccination effectiveness: (a) the number of weekly monkeypox cases reported by different countries and regions from March to July 2022; (b) the duration of monkeypox outbreaks in all regions of the world; (c) the relationship between the virus import and its duration of transmission; (d) changes in viral replication rate RT in North America; (e) Comparison of mean RT with cumulative percentage of people at high risk of vaccine immunization.
Vaccination has had a limited effect on containing the outbreakNext, the researchers focused on North America, which has the highest number of cases in the entire monkeypox epidemic, the impact of virus importation events on prolonging local outbreaks, and the impact of monkeypox vaccination on viral replication rate (RT). The data show that imported events only contribute about 5%-15% to local case transmission. Vaccination had a smaller impact on RT, and the researchers found that RT and the number of cases had already begun to decline in the early stages of the North American epidemic, before vaccination began in the United States(Figure 1d).。Prior to the advent of monkeypox vaccine-derived immunity in the United States, the North American RT reached 149。Assuming that RT decreases linearly as cumulative vaccine-derived immunity increases, the study predicts that RT will only fall below 33% after more than 1 percent of high-risk U.S. populations have developed immunity to monkeypox(Figure 1e, gray dotted line).。When the researchers compared the decay of actual RT in North America, they found that RT had fallen below 10 percent before about 10% of high-risk people developed immunity(Figure 1e, blue dot and solid red line)., which means that vaccination is not the main reason for the RT to drop below 1. Heterogeneity in the transmission of monkeypox outbreaksIn addition, the study found that a small number of transmission events resulted in a sustained expansion of local transmission, while most transmission events resulted in fewer downstream infections. Therefore, the measurement of the heterogeneity of virus transmission is very important for prevention and control efforts. The researchers observed characteristics of heterogeneity in monkeypox transmission. They found that multiple transmission events involving a small number of individuals had a much greater impact on the spread of an epidemic than most other transmission events. This suggests that the focus should be on these highly transmissible individuals to effectively control the spread of the epidemic. The study also highlights the importance of considering transmission heterogeneity when designing interventions, where priority should be given to highly transmissible and high-risk transmission events. Finally, the article points out the estimated results of transmission heterogeneity and offspring reproduction in different geographic regions, and how these results correlate with the structure of sexual contact networks in men who have sex with men. In conclusion, this study provides a new perspective and direction for understanding and controlling the spread of monkeypox. In summary, the study found that the monkeypox outbreak in 2022 spread rapidly among high-risk groups mainly through local occult transmission, and showed heterogeneity in transmission, and the containment effect of vaccines in North America was limited. The study highlights the importance of early outbreak surveillance and screening for the control of emerging infectious diseases. 
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References
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