A large number of papers have been published since the discovery of the monkeypox virus (MPXV). In 2022, human MPXV broke out in the USA and many European countries, and on July 23 of that year, the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern." In this study, we performed bibliometric analysis of MPXV literature published in core journals of the Web of Science core Collection database, which was conducted on 956 articles from 2000 to 2022. We analyzed the publication country, subject category, main authors and institutions, research hotspots of important publications and research frontiers. Through the analysis of keywords co-occurrence, multi-cited literature and co-cited literature, the research hotspots and trends were summarized. This report revealed that MPXV research has focused on hot areas such as infection and vaccination. Since the 2022 human MPXV outbreak, researchers have increasingly focused on infection control, vaccines, and treatment of monkeypox. This article summarizes the research directions and hotspots of MPXV related literature since the 2000, and we hope to provide support and clear research ideas for the future research and prevention of MPXV in humans.
Key words: monkeypox virus, bibliometric analysis, research hotspots
Monkeypox is a newly-developing zoonotic infection caused by monkeypox virus (MPXV) which has an incubation period of up to 21 days.[1,2] The MPXV is a large double-stranded DNA virus belonging to the orthopoxvirus genus, it is similar to Vaccinia virus and Variola virus. Monkeypox viruses are genetically of two distinct phylogenetic clades, one is the Central African clade, the other is West African clade. In endemic areas, various of mammalian species can carry MPXV, and periodically the transmission of the virus to human will take place. There are three potential routes of exposure to the virus, interaction with wild animals, close proximity to sick individuals, and contact with infectious fomites.[5,6]
Monkeypox was first reported by Preben von Magnus in 1958 in laboratory cynomolgus monkeys. The first human monkeypox virus infection was reported in Democratic Republic of Congo (DRC) in 1970. After that, MPXV infection was discovered in 11 African countries. The first MPXV infection out of Africa was in the USA, in 2003. We could speculate that the source of the 2003 MPXV infection in the USA was a shipment of rodents from West Africa. Before the 2017 outbreak of Nigeria, the MPXV has been reported to spread around the south and southeast of the country. During 2017 to 2018, 118 confirmed cases were reported in Nigeria. From 2018 to 2022, a number of cases of MPXV carriers from Nigeria spread to other countries, including Israel, the UK, Singapore, and the USA.[10,11,12,13] In 2022, the outbreak of MPXV in many European and American countries aroused the concern of the World Health Organization (WHO). On July 23, the WHO declared the MPXV outbreak a "Public Health Emergency of International Concern".
In this study, we performed bibliometric analysis of MPXV literature published in core journals of the Web of Science core Collection database, including number of national contributions, number of annual publications, number of institutions, number of authors, subject category, and keyword collinear. We intended to clarify the research trends and hotspots of MPXV through bibliometric analysis through this study, and also we hope to provide a new perspective and reference for future research and prevention of monkeypox in humans.
MATERIALS AND METHODS
Data Sources and Search Strategies
The data in this study were all from the Web of Science Core Collection database (WOS), with the topic of "Monkeypox" as the search strategy. The document type was limited to "Article", "Review Article" and "Meeting Abstract", and the language was "English". The publications were published in 2020 and 2021 (February) with articles and abstracts. The analyzed literature was published from January 2000 to October 2022, and the retrieval time is October 16, 2022.
Visual Analysis Method
This study adopted bibliometric method and scientific knowledge graph analysis. Bibliometric method is a comprehensive scientific method that uses statistical methods to quantitatively analyze the literature information resources retrieved.[15, 16] Online Analysis Platform of Literature Metrology (http://bibliometric.com) were applied for the presentation, analysis, and description of the data. Microsoft Excel 2020 software (Microsoft, Redmond, USA)) was used to visualize the annual publication by line graph. Scientific knowledge graph analysis was used to analyze countries/regions, research institutions, research hotspots and frontier hotspots, and to visualize the structure and development rules of discipline knowledge. CiteSpace 6.1.R3 software (Drexel University, Philadelphia, USA) was used to analyze the "keyword" node of the literature, and to explore the development context, research hotspots and frontiers of this field.
General Features of monkeypox Literature
From 2000 to 2022, 956 artic les related to monkeypox were indexed by the WOS in accordance with the search strategy, and 953 effective articles were obtained after using the CiteSpace 6.1.R3 software to remove the data, including 792 articles (83.1%) and 161 reviews (16.9%), no Meeting Abstract was included. The number of literatures related to monkeypox showed an overall increasing trend during the ten years from 2000 to 2010, and the number of literatures decreased from 2011 to 2021 compared with that in 2010, which showed a certain fluctuation. It is noteworthy that the number of articles published in 2022 has increased dramatically, with a total of 199 articles published before the retrieval date (Figure 1).
Figure 1: The publication year distribution of monkeypox related literatures included in the Web of Science Core Collection database from 2000 to 2022.
Figure 2 revealed the top 10 subject categories related to monkeypox research. Pharmacology & pharmacy and public environmental & Occupational health were the most frequent topics (Figure 2). Most of the research disciplines related to monkeypox were independent, but there were different degrees of overlap between public environmental & Occupational health with Pharmacology & Pharmacy and Biodiversity Conservation.
Figure 2: The top 10 subject categories related to monkeypox research.
Contributions of Countries to monkeypox research
The "country" nodes in CiteSpace 6.1.R3 software were used to analyze the country distribution of literature in the field of monkeypox from 2000 to 2022. There were 89 countries in total. The USA ranked first with 591 articles (62.0%), accounting for about two-thirds of the total number of articles published, and followed by Germany (82 articles [8.6%]), the UK (62 articles [6.5%]) and Republic of the Congo (53 articles [5.6%]). The top 10 countries/regions with the number of literatures were listed in Table 1. The USA cooperated with many countries around the world on monkeypox research, with Republic of the Congo being the leading partner (Figure 3).
Figure 3: Country cooperation in monkeypox research.
|Ranking||Country||Number of publications, n (%)|
|1st||The USA||591 (62.0)|
|3rd||The UK||62 (6.5)|
|4th||Rep Congo||53 (5.6)|
Institutions and Author with Research Publications on Monkeypox
The "Institution" node analysis showed that the top 10 research institutions with the number of published literatures on monkeypox were mainly located in the USA, Republic of the Congo and Germany (Table 2).
|Ranking||Institution||Country||Number of publications, n (%)|
|1st||Centers for Disease Control and Prevention||The USA||161 (16.9)|
|2nd||United States Army Medical Research Institute of Infectious Diseases||The USA||73 (7.7)|
|3rd||National Institute of Allergy and Infectious Diseases||The USA||62 (6.5)|
|4th||Saint Louis University||The USA||30 (3.1)|
|5th||Ministry of Health and Populations||Rep Congo||28 (2.9)|
|6th||SIGA Technologies Inc||The USA||23 (2.4)|
|7th||University of Kinshasa||Rep Congo||22 (2.3)|
|8th||University of Pennsylvania||The USA||22 (2.3)|
|9th||Robert Koch Institute||Germany||21 (2.2)|
|10th||United States Food and Drug Administration||The USA||21 (2.2)|
The analysis of "Institution" node showed that Centers for Disease Control and Prevention (the USA) (161 articles [16.9%]), United States Army Medical Research Institute of Infectious Diseases (the USA) (73 articles [7.7%]) and National Institute of Allergy and Infectious Diseases (the USA) (62 articles [6.5%]) were the institutions that published the most literature related to monkeypox research. Institutions with more than 10 publications were included in Figure 4, there was more cooperation among institutions and the cooperation network was relatively denser. Damon Inger K had the highest number of monkeypox related publications and the highest number of total citations. In addition, scholars such as Reynolds Mary G, Karem Kevin, Carroll Darin and Olson Victoria A have also published a large number of literature related monkeypox after 2000 (Figure 5).
Figure 4: Cooperative network of major research institutions for literatures.
Figure 5: Cooperative network of leading researchers for literatures concerning monkeypox.
Journals and Citations with Research Literatures on Monkeypox
A total of 953 English articles were published in 198 journals, and the top 10 journals accounted for 33.9% of the total articles included in this analysis. Among the top 10 journals publications on monkeypox (Table 3), Journal of Medical Virology with impact factors (IF), IF (2021) = 6.549, had the most published (n = 50), followed by Vaccine (n = 46; IF  = 4.169), Plos One (n = 42; IF  = 3.752), and Viruses-basel (n = 40; IF  = 5.818).
|Ranking||Journal||Number of documents||IF*||Country|
|1st||Journal of Virology||50||6.549||The USA|
|3rd||Plos One||42||3.752||The USA|
|6th||Emerging Infectious Diseases||28||16.126||The USA|
|8th||Journal of Infectious Diseases||20||7.759||The USA|
|9th||Antimicrobial Agents and Chemotherapy||19||5.938||The USA|
|10th||Virology Journal||18||5.916||The UK|
|*Impact factor (IF) based on Clarivate Analytics Journal Citation Reports (JCR) 2021.|
The citation counts for the top 10 articles ranged from 235 to 404 (Table 4). These documents were published in 7 different journals. The most cited article about the use of publications on monkeypox worldwide was the detection of monkeypox in humans in the Western Hemisphere, which was published by Reed, Kurt D in the USA, and this article was cited 404 times.
|Title||Corresponding authors||Journal abbreviation||IF*||Publication year||Total citations|
|The detection of monkeypox in humans in the Western Hemisphere||Reed, KD||New Engl J Med||176.082||2004||404|
|The role of evolution in the emergence of infectious diseases||Antia, R||Nature||69.504||2003||344|
|Pathways to zoonotic spillover||Plowright, Raina K||Nat Rev Microbiol||78.297||2017||341|
|Poxvirus ropism||McFadden, G||Nat Rev Microbiol||78.297||2005||303|
|Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox||Moss, B||Nature||69.504||2004||272|
|A preliminary assessment of silver nanoparticle inhibition of monkeypox virus plaque formation||Rogers, James V||Nanoscale Res Lett||5.418||2008||271|
|Poxvirus genomes: a phylogenetic analysis||Smith, GL||J Gen Virol||5.141||2004||258|
|Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo||Rimoin, Anne W||P Natl Acad Sci Usa||12.779||2010||243|
|Current concepts - Diagnosis and management of smallpox||Breman, JG||New Engl J Med||176.082||2002||241|
|Panmicrobial oligonucleotide array for diagnosis of infectious diseases||Lipkin, W. Ian||Emerg Infect Dis||16.126||2007||235|
|*Impact factors (IF) based on Clarivate Analytics Journal Citation Reports (JCR) 2021.|
Analysis of Keywords About Research Literatures on Monkeypox
The keywords chosen by article authors when they submitted their manuscripts for publication were extracted with CiteSpace 6.1.R3. We analyzed the keywords extracted from 953 publications, defined as terms that occurred more than 10 times within titles and abstracts in all articles during the analysis. In total 108 keywords were included in the keyword co-occurrence network (Figure 6). The circle nodes represent the keywords, the size represents the frequency of occurrence, and the color changes of the node circle indicate the year, and the light to dark reflected the year of publication from far to near.
Figure 6: Keywords co-occurrence network about research literatures on monkeypox.
Log-likelihood (LLR) clustering was used to analyze the keywords of monkeypox related literatures monkeypox research, and the research hotspots of monkeypox research was visualized and presented in the way of network visualization. The results show that, Q = 0.7276 > 0.3000, S = 0.9221 > 0.500, indicating that the effect of clustering map was better. Figure 7 shows the top 10 most used topic clusters, with purple to red indicating the intensity of the clusters and arrows indicating the trends of hotspots. As shown in timeline view of keyword research hotspots, skin lesion, monkeypox virus, sexual health, viral shedding were new keywords in 2022 (Figure 8).
Figure 7: Clustering diagram of keywords in literatures concerning monkeypox.
Figure 8: Timeline view of keyword research hotspots.
Seventeen keywords with the strongest citation bursts from 2000 to 2022 were highlighted (Table 5). Keywords with the End year of 2022 were disease outbreak, zoonotic disease, infectious disease, and host range (Table 3). Combined with Figure 6, the research frontiers of monkeypox were monkeypox outbreak, human infection with monkeypox virus, the spread range of monkeypox.
|Order||Keywords||Strength||Begin year||End year|
|3||Severe acute respiratory syndrome||1.87||2005||2006|
|6||Modified vaccinia virus ankara||2.76||2007||2010|
|13||Democratic republic of congo||2.20||2017||2019|
Monkeypox is a zoonotic orthopoxvirus which has predominantly affected humans living in western and central Africa since the 1970s. The first outbreak outside the continent was occurred in the USA in 2003. In September 2017, human monkeypox infection re-emerged in Nigeria. Isolated cases of monkeypox virus infections had been found in Israel, the UK and Singapore from 2018 to 2020.[3,4] Since May 2022, human monkeypox had erupted in multiple countries, with a total of 21,098 cases of human monkeypox reported worldwide, spanning across 41 non-endemic diseases with a high number of cases and no direct link to endemic countries.[16,17]
In this study, from the annual number of papers published, the number of literatures published before 2022 was small, with only a few years with more than 50 literatures published. There was a small peak in related literature reports from 2003 to 2005, possibly associated with the June 2003 outbreak of monkeypox in the Midwest of the USA. Seventy one cases of monkeypox had been reported from 6 states and human infections were associated with direct contact with ill pet prairie dogs.[1,2] Of the top 10 cited literatures, 9 were published in 2010 or before, with the majority coming from the USA. Since 2000, most monkeypox research has been conducted in pharmacology and pharmacy, with A and D being the most prolific authors in this field, Damon Inger K, Carroll Darin and Reynolds Mary G, Mccollum Andrea were the most published scholars in these two fields respectively. In addition, researchers such as Shchelkunov Sergei, Jahrling Peter B, Buller R. Mark and Rimoin Anne W had conducted monkeypox related research in other disciplines, respectively, these researchers may be the leading in the field of monkeypox research.
The USA has a long history of research in monkeypox, with 62% of the literature published after 2000. The top 3 countries with the most publications were the USA, Germany and the UK, reflecting their influence in monkeypox research. Centers for Disease Control Prevention (the USA) was the most published institution and the most frequently cited institution, and cooperated with almost all influential scientific research institutions in the field of monkeypox research, including Ministry of Health and Populations (Rep Congo) and Robert Koch Institute (Germany). It shows that international cooperation is necessary and will be the trend in the future in the treatment and prevention of monkeypox. Our results showed that the Journal of Virology, Vaccine, and Plos One were among the top 3 journals. The Journal of Virology has published the most literature related to monkeypox, and it was also the most frequently cited, indicating that monkeypox was of great value in virology research field.
Our study showed that since 2000, monkeypox research had mainly focused on the frequently occurring keywords such as vaccinia virus, monkeypox virus, smallpox vaccine, emerging infectious diseases, communicable diseases, etc. In 2022, new keywords such as infection control, vaccine hesitancy, molecular dynamic simulation, monkeypox treatment and healthcare system appeared in the field of monkeypox research, indicating that research on the treatment and control of monkeypox will be a research hotpot in the next few years. The reasons for change in keywords on monkeypox may be as follows. Firstly, the rapid increase of cases around the world has brought greater attention to disease control and treatment. Secondly, sexual transmission, especially same-sex transmission, has attracted much attention.
According to the epidemic statistics of monkeypox released by the WHO on August 31, there were 50,496 confirmed monkeypox cases in the world, and the Americas has the highest number of monkeypox infections in the world, with more than 60% of cases occurring in the Americas and about 30% in Europe. Several studies had shown that the 2022 outbreak of monkeypox virus belongs to the same lineage as the 2018 monkeypox virus strain, illustrating the genomic evolution of the ongoing MPXV outbreak. Compared with the monkeypox virus strain in 2018, in total 46 new consensus mutations were observed in the MPXV-2022 strains, including 24 nonsynonymous mutations. Another study showed 15 single nucleotide polymorphism sites, secondary variants and gene deletions appeared. These microevolutions showed signs of better adaptation to the human body. Most cases of monkeypox have occurred in men, mostly homosexual, bisexual, and other men who have sex with men (MSM). Among the MSM cases, many of them presented atypical clinical manifestations of monkeypox and with other sexually transmitted diseases co-infection. Therefore, in this outbreak, some cases were misdiagnosed as herpes simplex virus or varicella zoster virus infection. Regarding the high social interactivity in MSM, there is a relatively higher risk of monkeypox transmission in this population.
Case reporting, epidemiological investigation, laboratory testing, isolation and treatment of cases and close contacts are important components in controlling the spread of monkeypox. As the incubation period of monkeypox virus ranges from 5 to 21 days, 21-day quarantine of suspected infected individuals is a necessary measure to reduce contagion. National Health Commission of the People’s Republic of China has recommended and adopted a 21-day quarantine for suspected or confirmed cases. Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Most patients recover without medication. WHO recommends that clinical care focus on alleviate symptoms, manage complications and prevent long-term sequelae. Certain antiviral drugs have been shown to be effective against human monkeypox infection. An oral antiviral drug-tecovirimat, was approved as an investigational New drug (EA-IND) for the clinical treatment of human monkeypox in the USA in 2022, at the meantime the drug was officially approved by The European Medicines Agency and the UK for the treatment of human monkeypox virus using the same animal studies reviewed by the U.S. Food and Drug Administration (FDA).[24,25] However, the access of the drug is still extremely limited, and more data on its efficacy and safety remains to be clinically tested and verified. For populations in high-risk areas, vaccination remains the primary measure for the prevention and control of human monkeypox. Some countries are adopting or exploring policies to provide vaccines to people who may be at risk, such as laboratory personnel and health workers. Vaccination against smallpox was demonstrated in preventing monkeypox, and unvaccinated people were more likely to become infected with human monkeypox virus. While the first-generation smallpox vaccine used in the smallpox eradication program had been discontinued, the development of second- and third- generation smallpox vaccines driven by concerns about smallpox as a biological weapon. The FDA has approved two vaccines in the USA, ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) that can prevent human monkeypox. However, the development of an effective and safe new generation human monkeypox vaccine is extremely necessary due to the serious complications that may result from vaccination of ACAM2000 and JYNNEOS.[28, 29] Establishing rapid diagnostic testing and laboratory response networks for surveillance and rapid detection of new cases is an important part of controlling monkeypox outbreaks. It is essential to investigate the source of this outbreak, to study all possible modes of transmission and to limit further spread. Raising awareness of risk factors and educating people about what can be done to reduce exposure to the virus are the main prevention strategies for monkeypox. Surveillance and rapid detection of new cases are essential to contain the outbreak.
This study conducted bibliometric analysis of monkeypox related literatures published from 2000 to 2022 based on Web of Science Core Collection database. In the past 22 years, monkeypox research has mainly focused on such hotpots as infection and vaccination. Since the outbreak of human monkeypox in 2022, researchers on this tend to pay attention to infection control, vaccine and monkeypox treatment. Contact tracing, testing, surveillance, and vaccination are the main measures to contain human monkeypox outbreak. Controlling the spread of monkeypox is of top priority, but how to deal with the relationship between human and nature may be the deep thinking brought by the outbreak of human monkeypox virus as a zoonotic disease.
Wu X, Tang S and Zhang Z designed the study and revised the manuscript. Tan J, Zhang Z and Yuan Y collected the data. Zhao Y, Lin X, Ning J, Zhang Z and Yuan Y did the statistical analysis. Zhang Z and Yuan Y prepared the manuscript.
Conflicts of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Source of funding
This work was supported by grants from the Natural Science Foundation of Zhejiang Province (No. LQ21H190004) and Huzhou Municipal Bureau of Science and Technology (No. 2020GZ43). The funding sources had no role in the study design; in the writing of the report; or in the decision to submit the paper for publication.
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