Our study has produced an up-to-date and in-depth exploration of the focuses and development trends of hantaviruses and hantavirus diseases in the past 40 years through VOSviewer and CiteSpace, and visualize knowledge structure about the relationships of related countries, institutions, authors, keywords and references with many bibliometric analysis methods in two novel bibliometric analysis software systems, providing a basis for future research in this field.
The trend analysis indicated three major stages of research on hantaviruses: the first stage was from 1980 to 1994, the second stage was from 1995 to 2014, the third stage was from 2015 to 2019. The number of publications increased slowly from 1980 to 1992, and rapidly grew from 1992 (44 publications) to 1994 (128 publications). The second stage had variable numbers of publications over time, but the number of publications increased significantly from 2012 to 2014. The rapid growth in the number of publications during the first and second stages might due to the two major outbreaks of hantavirus diseases: HCPS in the “Four Corners” area of the United States during 1993 and HFRS in Germany during 2012 [11, 32, 33]. These publications appeared 1 to 2 years after the outbreaks. Research on hantaviruses has always been a hot spot in the United States and European countries. However, research on this topic is becoming increasingly more common in China, indicating that Chinese researchers are paying more attention to this topic.
According to the distribution of countries/regions, These results indicated the United States was the most productive and cooperative country, probably because HCPS was classified as a notifiable disease in the United States in 1995, and hantaviruses-related studies have received significantly more attention over time [29,30,31, 34]. Among all analyzed publications, 2927 publications were published in the United States, China, Germany, Finland, Sweden, and France. The United States, China, Germany, Finland, Sweden, France, Argentina, Japan, and Brazil were at the center of an international co-authorship network, suggesting that these countries are the current leaders in research on hantaviruses (Figs. 3 and 4A). Also, these countries are the main endemic areas of hantaviruses. In recent decades, most reported infections with hantaviruses are in Asia, but the number of cases in the United States and Europe has increased . China and Brazil are the most active countries, suggesting that related cases has increased considerably over the past decade in these countries, becoming a severe public health problem. Figure 4A also shows that cooperation of countries/regions that have greater geographic proximity and cultural similarity is close, such as Sweden has more close cooperation with Finland than China. Therefore, it is strongly suggested that different geographies with different cultures should strengthen cooperation.
We found that 4 of the top 10 most productive institutions were in Europe, and 3 was in Asia. These 7 institutions focused on the HFRS, or nephropathia epidemica (NE). The other 3 top institutions were in the United States, and mainly studied HCPS. The top 10 institutions were near the core of each cluster in a map of co-authorship, indicating that these institutions lead the research trends in this field (Fig. 4B). Among the top 10 authors, 5 were from Europe, 3 were from the United States, and 2 were from Asia (Tables 3). Among all 12,529 authors, 727 published more than 5 papers in this field. The cooperation between two authors within the same co-author cluster was common, but there was much less cooperation between authors in different co-author clusters (Fig. 4C). This indicates that although many authors and institutions were interested in research on hantaviruses, collaborations among disparate authors and institutions was limited. Promoting more collaboration between disparate authors and institutions may improve the quality and increase the number of studies on hantaviruses.
We found that 6 of the top 10 journals and co-cited journals were from the United States, indicating that these journals made the most contributions and attracted the most attention. In addition, high-IF journals had more co-citations (Table 2), suggesting that these journals had the most important roles in studies of hantaviruses. The dual-map overlay of journals (Fig. 5) indicated that the relationships between journals and co-cited journals were responsible for the main research directions, thus providing indispensable information for researchers new to this field.
Seven of the top 10 most frequently cited references were published in 1994 or later. This is consistent with our findings that the number of publications increased rapidly during this time (Fig. 2A) and also indicates that the worldwide understanding and recognition of hantavirus infections has greatly increased since 1994. Bibliometric analysis of references and co-citations (Fig. 6) showed that there were 4 clusters representing basic areas of research: structure and function of hantaviruses; identification of hantaviruses; clinical symptoms and pathophysiologic studies of hantavirus diseases; and ecology and epidemiology of hantaviruses.
The focuses and frontiers
Keywords summarize research focuses and core content of publications. Based on keyword co-occurence analysis, it possibly provides a way to learn about the distribution and development of different research focuses in a specific field. Keywords cluster analysis was conducted on the basis of co-occurence, and finally three clusters were formed.
According to cluster analysis (Fig. 7)and the time-zone analysis (Fig. 8), we determine main research focuses and frontiers in this field. The main contents are as follows:
HFRS and related research
Hemorrhagic fever with renal syndrome (HFRS), characterized by renal failure and haemorrhagic manifestations, is mainly caused by HTNV, SEOV, and several recently discovered species of hantaviruses . The clinical symptoms of HFRS varies from subclinical, mild, and moderate to severe, depending partly on the causative serotype of the hantaviruses. In general, the clinical characteristiccs caused by HTNV or DOBV are more severe, whereas SEOV causes moderate disease and PUUV cause mild forms of disease [10, 36]. According to the latest report, there are about 15,000 to 20,000 HFRS cases worldwide annually, and the fatality rate ranges from 1 to 12% [10, 11]. Most infections are in the Asia–Pacific region and Europe, and this disease has become a serious threat for public health, especially in China . A recent study reported almost 20,000 cases per year in China , and this accounts for more than 90% of the reported cases worldwide . Apodemus agrarius and Rattus norvegicus are the main reservoir hosts for HFRS in wild and residential areas, respectively . Rapid economic growth, urbanization, and climate change may have increased the transmission of this zoonotic disease by increasing rodent populations, and these factors may be the important influence effects in this field. Great changes have occurred in areas where there are epidemics, new epidemic areas have emerged, and endemic areas have gradually increased. To our knowledge, only a few inactivated vaccines are currently used in China and South Korea, and there is no universally licensed vaccine for HFRS . In addition, there are no specific treatments for this disease, and most clinicians recommend supportive care.
HCPS and related research
Hantavirus cardiopulmonary syndrome (HCPS), characterized by pneumonia and cardiovascular dysfunction, was first reported in the United States . Initial research reported that HCPS was characterized by severe, acute cardiopulmonary failure, and reported more than 1,000 cases. Compared with HFRS, HCPS is a more severe disease with a fatality rate from 35 to 50% [42, 43]. The clinical presentations of HCPS generally are three phases: prodromal, cardiopulmonary and convalescent, and clinical syndromes can vary from mild hypoxaemia to respiratory failure with cardiogenic shock . SNV and ANDV are the two major causative agents, and approximately 43 strains of these viruses were reported in the Americas, 20 of which can cause HCPS. SNV is the most prevalent hantavirus genotype in North America (United States and Canada), and deer mice (Peromyscus maniculatus) are the predominant rodent reservoir. ANDV is the major cause in South America (Chile and Brazil), and this hantavirus is unique because person-to-person transmission is possible, and this has posed a major challenge to the health care systems of Argentina and Chile [45,46,47]. Recent research in Germany indicated that PUUV caused HCPS . At present, there are also no specific treatment measures for HCPS.
NE and related research
Nephropathia epidemica (NE) is a mild form of HFRS, which mainly occurs in Europe, and is characterized by acute renal failure and thrombocytopenia [49, 50]. The occurence of thrombocytopenia in this type of disease varies from 39 to 98%, whereas bleeding complications are rare in acute NE . It is also reported that smokers acquire more severe kidney than non-smokers . NE was discovered in Sweden during the 1930s , but the pathogenic virus (PUUV) was first identified in bank voles (Clethrionomys glareolus) in Finland during 1980 . A 2014 study reported that thousands of human hantavirus infections occurred annually, and the number of NE cases has increased during recent years due to climate change and economic development in Europe . Although several hantavirus species are circulating in Europe, such as Dobrava virus, Saremaa virus, and Tula virus, PUUV is by far the most prevalent species . As with other diseases caused by hantaviruses, there are no specific treatments diseases caused by these species, and only supportive care is used.
The changes of research frontiers
Our time-zone map of the top 20 keywords of each slice (Fig. 8) indicated that most of the initial research on hantaviruses focused on clinical symptoms and the cause of this type of disease before 1990. After then, research on identifications of serotypes of hantaavireses, such as hantaan virus, puumala virus., and pathogenesis of these diseases probably have become research frontiers in this field from 1990 to 2000. And there was a great increase in this research during the 1990s, in line with our conclusions above. From 2000 to 2010, studies on the correlations between the characteristics of diseases and the evolution of the pathogens, the transmission of these diseases have received more attention. Research on the factors affecting the prevalence of the diseases, vaccine and factors affecting the distributions of host animals have been research frontiers in this field in the past decade. Our results suggest that future studies will focus on the characteristics and distributions of hantavirus diseases, the discovery of new species, the development of vaccines, and factors that affect the distribution and density of rodent host populations.