Introduction
Monkeypox is a zoonotic disease caused by infection with monkeypox virus (MPXV), which is endemic in Western and Central African countries. The current re-emergency since 7 May 2022 has been reported to influence at least 104 historical non-endemic countries in Europe (45 countries), America (31 countries), Asia (18 countries), Africa (13 countries) plus Oceania (4 countries), even causing 127 human deaths in 17 countries outside its previously reported endemic areas [
1‐
3].
Novel mode of transmission, sexual transmission for the most part of infections (97.52% of the reported cases come from population of men who have sex with men), was distinct from previous interregional transmission such as travel-related importation from Africa or exposure to infected exotic pets [
3,
4]. Considering its spread around the world rapidly through new modes of transmission and limited knowledge about it, the World Health Organization (WHO) has declared monkeypox a Public Health Emergency of International Concern (PHEIC) on July 23, 2022, which is the highest level of alert issued by the global health body [
1,
5,
6].
Against this background, several queries remained to be addressed before national and global responses can be developed. Whether or not the spread of monkeypox is driven by a rise in the number of cases at the source in Western and Central Africa, how is the increased frequency of travel to and from endemic areas in Africa or epidemic areas in Europe was linked to the exported infections? And where might future outbreaks strike? Recent studies indicate the ecological niche of MPXV in Western Africa has spread across known ecological areas e.g., from the freshwater swamps and mangrove areas to savannah vegetation areas in the Nigeria 2017–18 outbreak, which call for further study by using updated data to might alter or refine niche modeling results [
7]. In addition, the changing pattern of case predominance in urban areas indicated by the recent ongoing outbreaks may suggest the possibility of MPXV transmission from humans to local animal reservoirs, with in long-term consequences that should be further explored. This is a crucial concern for estimating the population at risk and for future public health measures.
Here by combining data from literature review and officially released reports, we assembled a dataset that contained all MPXV infections reports of both human and non-human sources since 1958 when the virus was identified [
8]. A variety of environmental, socioeconomic, and biological factors were collected and applied in the model construction to predict areas at risk of monkeypox outbreaks. The inter-regional transmission risk of MPXV has also been examined by using the data from global annual air travel flows of origin–destination.
Discussion
By combining spatial–temporal and phylogenetic data on MPXV, we mapped the global distribution of MPXV infections in humans and animals, defining populations at risk from zoonotic transmission or travel-related infections, thereby providing a robust framework for assessing its global impact. Since its introduction in 1970, a total of 49 432 human cases of MPXV infections have been reported, primarily in Central Africa and Western Africa until 2022, with occasional travel-related cases in other countries and an animal trade-related outbreak in the United States in 2003. The current outbreaks associated with the West African clade have milder disease severity and resulted in less fatalities, however, remains as a serious concern when considering the marginally increased R
t from 2000–2009 to the most recent decade, indicating an elevated transmissibility. The international connectivity by airline traffic posed another severe concern, many Europe countries especially those in West Europe have a high risk of travel-related infections both from endemic and current epidemic countries, and three cities (Chongqing, Beijing and Guangzhou) in China have reported five MPXV cases [
26], indicating that more attention should be paid to the spillover and human-to-human transmission, and if it continuously spreads, it will be a shock to the vulnerable global health system during the COVID-19 pandemic [
27].
BRT models reveal that ecological niche of MPXV was significantly associated with four ecoclimatic factors, such as annual precipitation, min temperature of coldest month, isothermality, and annual mean temperature, as well as three reservoirs-related factors, including the predicted distributions of
Graphiurus lorraineus and
Graphiurus crassicaudatus, and the richness of Rodentia. Ecoclimatic factors may lead to an increase in MPXV infections in humans from zoonotic transmission. Precipitation can affect the behavior and movements of reservoir hosts of MPXV. For example, heavy rainfall can lead to changes in the distribution of water sources, affecting the movement patterns of rodents and their interactions with each other and other animals (e.g., non-human primates) [
28]. The min temperature of the coldest month, isothermality, and annual mean temperature may affect the activity and reproduction of reservoir hosts, the survival and transmission of the virus, and the overall risk of disease outbreaks [
29]. This climatic-driven zoonotic spillover potentially generated by human activities such as deforestation, combined with agricultural activities and hunting in forests, may contribute to the spread of monkeypox in endemic areas [
30].
Ecological drivers are part of the complex interrelationship between humans, animals, and the environment during the zoonotic transmission of MPXV. Four rodent reservoirs were used to build the model, two of which (
Graphiurus lorraineus and
Graphiurus crassicaudatus) were included in the final model, revealing a highly correlation with the zoonotic niche of MPXV. The negative trend between rodent richness and MPXV ecological niche suggests that the dilution effect may apply to the MPXV distribution [
31], as a high richness environment may reduce the activity of reservoir rodents, and consequently reduce the ecological niche of MPXV, which has also been observed in Lassa fever [
32]. It is important to note that the inclusion of these rodent species and the overall richness of Rodentia in the analysis highlights the importance of studying rodents and their role in zoonotic diseases. Our study indicates that researches about rodents should not be ignored due to the vital roles of rodents in many zoonotic diseases, e.g., Lassa fever and human infection with hantaviruses that have persistent threats to global health [
33,
34]. There is still a hypothetical risk of human-to-animal transmission, and it is worth focusing on those areas outside Africa where our model projects highly suitable environments for MPXV occurrence, avoiding the colonization of the virus in animals. Rodentia animals have been intensively reported to harbor MPXV, our study highlights the association between African dormice (
Graphiurus spp.) and MPXV niche, and other studies have revealed that rope squirrel (
Funisciurus spp.) showed the overlap niche with MPXV [
35]. These results contribute to natural advantages in viral connectivity or horizontal transmission within reservoir rodents, promoting virus sharing and dissemination among these hosts [
36]. Collectively, these insights contribute to our understanding of the complex ecology of MPXV transmission dynamics.
Our model predicted potential ecological niche of the MPXV throughout the Congo Basin and Western Africa, including parts of the DRC, Nigeria, Congo, Côte d'Ivoire, and some areas without reported cases, e.g., Ethiopia, Kenya, and Guinea. Some areas are lack of efficient surveillance network of MPXV infection in animals or clinical patients, in where under-reporting due to limited field investigations or laboratory identification might contribute to its continuous transmission among humans, until outbreaks were noticed [
37]. The international community could consider to allocate resources to strengthen surveillance, laboratory testing, case investigation and contact tracing, clinical management, vaccinations and immunization, and risk communication in these countries.
The unprecedented and unexpected outbreaks outside Africa since May 2022, have attracted the focus of global public health systems and have been issued as a PHEIC by WHO [
6,
38]. Based on our updated estimates of the transmissibility, the effective reproduction number in European countries (e.g., Germany, France, and Switzerland) since May 2022 is greater than 1, indicating a probable increase in its transmissibility. Countries experiencing higher R
t values need to consider implementing or intensifying targeted interventions, such as increased surveillance and case detection, contact tracing, isolation and quarantine measures, public awareness campaigns, and vaccination programs where available. In addition, monitoring changes in R
t can reveal the impact of specific interventions and policy implementations, allowing for timely adjustments of control strategies as the outbreak evolves [
39,
40]. For countries at a higher-imported risk, e.g., the United Kingdom [
3,
41], the United States [
41], South Africa [
42], and Saudi Arabia [
43], measures to increase the sensitivity of case detection are helpful for the control of the disease. As global routine measures of prevention and control of the COVID-19 pandemic were made, the demand for gatherings is increasing day by day. Although the role of MSM transmission in the spread of monkeypox cannot be ruled out at this time [
14,
44‐
47], clustered cases may occur in any group that has been in close contact in a large-scale gathering event. Continuous outbreaks of 2022-monkeypox have revealed significant gaps in understanding the mechanisms of viral transmission and the continuously changing epidemiological characteristics of the disease, and a more integrated approach to epidemic preparedness is long overdue.
The study is subject to several limitations. First, the epidemic status of monkeypox in Africa may be underreported due to weak medical and health conditions in some countries. Second, although smallpox had been eliminated in the world and the smallpox vaccination had been stopped in the 1980s [
48], good cross immunizations between smallpox and MPXV have been reported, we did not consider the susceptibility of populations to monkeypox in the analysis of inter-regional transmission of MPXV, which might overestimate the risk of interregional transmission.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.