A Bibliometric Analysis of Global Scientific Research on Scrub Typhus

Objective The rise of zoonotic diseases has become a global health issue around the world. The present study is aimed at assessing the global status and the trends in scrub typhus (ST) research. Methods Publications related to ST studies from 1945 to 21st July 2020 were retrieved from the Scopus database. The search for the ST literature was conducted using the entry terms of the MeSH (Medical Subject Headings) database. Full research articles and reviews were included in the analysis, and no limitation to the language was specified. Key bibliometric indicator analysis was performed using Microsoft Excel, Bibliometrix (an R package), GraphPad Prism 5, and VOSviewer (version 1.6.6). Results A total of 1567 publications were retrieved. The results revealed a significant increase in the number of ST publications over time. The documents received an average of 11.22 citations per document. Mahidol University in Thailand (258, 16.46%) was the most productive institution, while the American Journal of Tropical Medicine and Hygiene published the most ST articles (88, 5.62%). Korea (195, 12.44%) was the most productive country, followed by India (178, 11.36%) and China (106, 6.76%). Richards AL was the most productive author with 36 articles. Conclusions The study findings provide useful insights into the global efforts and works related to the progress of ST research, which can be used to identify future research areas, such as vaccine development.


Introduction
Scrub typhus (ST) is a vector-borne disease carried by the chigger mite [1]. It is endemic to numerous countries in the Asia-Pacific region [2]. It is considered the most critical vector-borne infection associated with travelers [3,4] and has a higher incidence rate among the farmers than the nonfarmers in rural areas [5]. In addition, ST is a significant health issue among military personnel [6].
Up to date, more than one billion people worldwide are at risk of ST, and one million cases occur annually, especially in areas with limited access to health care services [7], which needs to be targeted via public health interventions [5]. The epidemiology of the disease traces back to World War II [8], and it is reemerging in many Southeast Asian countries [7]. Previously, it was endemic in a specified area mainly known as the "Tsutsugamushi Triangle" [2]. However, it is no longer restricted to the Tsutsugamushi Triangle [9].
In the past years, there have been significant scientific revolutions in ST research, specifically in fields that identify the ST patients' complications, treatment, diagnosis, and prevention [10,11]. Thus, many documents have focused on the genotypic diversity of O. tsutsugamushi in the world, promising potential resources for diagnosis as well as the development of vaccines [2,12,13].
Therefore, we employed the concept of bibliometric analysis as a tool that uses scientific databases to draw relationships among academic journal citations and deduce trends and research directions within specific topics. The concept provides a better understanding of the aspects of science through systematic analysis of authors and journal citation reports [14,15]. This bibliometric analysis, therefore, is aimed at assessing the global status and the trends in scrub typhus (ST) research, from 1945 to 2020.
The results of this analysis could help not only to provide an overview of ST publications based on predefined criteria (such as countries/region, institutions, productive authors, and journals, among others) but also assess the characteristics of ST publications.

2.
1. Data Sources. The data used in this study was obtained from the Scopus database (http://www.scopus.com/) through a comprehensive online search of ST documents published between 1945 and 2020.

Search Strategy. All the ST-related publications from
Scopus were collected on a single day (on 21 st July 2020) to avoid the daily update of the database. Moreover, the Scopus database provides the highest scientific quality of publication in comparison with other databases [14,15]. In our study, an extensive search was done using Medical Subject Headings (MeSH), which imposes uniformity and consistency to the indexing of the biomedical literature (https://meshb.nlm.nih.gov/search). We used the search terms as follows: title (Orientia AND tsutsugamushi AND infection) OR title (tsutsugamushi AND disease) OR title (tsutsugamushi AND fever) OR title (scrub AND typhus), as shown in Figure 1. Regarding manuscript types, the search was restricted to only "article" and "review." Two reviewers (THM and JK) independently screened the title to compile a list of the top 10 mostcited articles of scrub typhus. There is no ethical approval required for this study since there was no direct contact with human or animal subjects involved. Finally, the resulting bib.txt data was downloaded from Scopus, and as a result, 1567 publications related to ST were the subject of further analysis.

Data Collection.
The following data were extracted from the retrieved publications: title, year of publication, author details, country, institution, journal, and number of citations, among others. This was used to evaluate citation density (i.e., an average of the number of citations received per year and per article), annual trend of publications, most productive authors, institutions and journals, and country contributions.

Data Analysis and Data Visualization.
The key bibliometric indicators were analyzed using Bibliometrix, an R package, and these included the following: publication trends, citation scores, top 10 authors, journals, institutions, funding agencies, and cooccurrence of keywords, among others. GraphPad Prism 5 was used for time trend statistical analysis [16]. Map construction, cooccurrence network analysis, and visualization were conducted using the VOSviewer (version 1.6.6) package program (Leiden University, Leiden, The Netherlands). The program is freely available (https:// www.vosviewer.com).

Results
3.1. Publication Output and Document Types. From the search criteria, a total of 1567 ST documents were identified, of which research articles dominated (1499, 95.66%) followed by review papers (68, 4.34%). When assessing the number of publications by language, most were published in English (1337, 85.32%), followed by Japanese (122, 7.78%) and Chinese (51, 3.25%), while other languages included Russian, Korean, Dutch, German, Italian, and Spanish, among others (57, 3.64%).   Table 1 shows the top 10 papers cited in ST research ordered by the total number of citations. The top 10 papers contributed to 1596 of the total citation scores. Among the top 10 articles, 5 articles were published as literature reviews and 5 as full research articles. The article by Watt and Parola [17] published in 2003 entitled "Scrub Typhus and Tropical Rickettsioses" was the most cited (n = 254 citations) and was published as a literature review. Of the top 10 highly cited articles, two [2,18] were published in the journal of Clinical Infectious Diseases, which holds an impact factor IF = 8:313, and one [10] in Lancet with an impact factor of IF = 60:392.  Figure 3. Based on our Scopus data, the most productive journal was the American Journal of Tropical Medicine and Hygiene with 88 (5.62%) documents, followed by the Journal of the Japanese Association for Infectious Diseases (53, 3.38%) and PLOS Neglected Tropical Diseases (43, 2.74%), among others.   1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 Table 4.

Coauthorship Analysis and Collaboration between the
Countries. The coauthorship network is presented in Figure 4 using VOSviewer. A threshold of two links (collaborations) was applied, which resulted in a total of 34 countries meeting the criteria.     Figure 6 shows the most collaborative institutions of ST research. A minimum of 3 organizations was set, and 75

Discussion
Scrub typhus research has expansively increased during the last ten years, and the rapid growth in seroepidemiological data of Orientia tsutsugamushi infection has been reported from the area of the Tsutsugamushi Triangle [2,9]. The growth of ST publications could be attributed to several factors like the emergence of new ST cases around the world [2,5,9], amidst no licensed vaccines to date nor effective vector control efforts across the world [19]. Despite the international efforts in reducing the risk factors and increasing awareness in endemic regions, the public health burden and global distribution of ST remain poorly known in the world [19]. Furthermore, ST is an unrecognized zoonotic disease with a significant burden on public health and economic status [20]. The present study shows that the earliest record was published in 1945 and discussed the epidemiology and control of ST disease that occurred during the Second World War [21]. Since 1985, the number of scholarly published ST documents has increased steadily [3,4,8,12,13], and the use of molecular epidemiology and genetic characterization techniques [22][23][24] has led to a better understanding of the research gap in Orientia tsutsugamushi. ST is a global public health problem within the area of the Asia-Pacific region, which can cause extensive endemic problems for people living in India, Korea, Taiwan, Sri Lanka, the Philippines, Thailand, and China [3,7,10,12,22].
There are more than 1567 ST articles that have been published in the 491 most prolific journals indexed in the Scopus database. These reported journals have created a scientific forum for researchers to discuss the hot themes in the field of ST. The involvement of these journals is a sign of the importance of ST topics to the scientific community in the world.
Analysis of the most productive authors and countries enables researchers to point out the link strength between the documents published and identify future research trends basing on coauthorship, productive authors, and organizations.
The top 10 most-cited documents were published in medical journals. A large impact factor of journals indicates that the articles in the journal obtain, on average, a more significant number of citations and top-cited papers usually appear in journals with high impact factors [25].
The analysis of the top-cited articles indicated that ST research covered various key aspects such as ST geographical distributions and genetic diversity, serological diagnostic, clinical image and disease complication, and ecology of chigger-borne infections, among others. Notably, the two top-cited documents by Watt and Parola [17] and Kelly et al. [2] both describe ST as a significant public health problem in tropical regions. They also present a clear picture of the geographical distribution and genetic diversity of the disease [2,17]. Thus, the brief overview of the top 10 ST documents highlighted more insights into the research directions that highlighted hotspots and promising avenues for future research work in the ST field.
Furthermore, from the evidence of the geographical distribution map, it indicated that ST cases and research production were not restricted to the Tsutsugamushi Triangle [2]. The emergence of ST pathogens and scientific research production included other countries in the world [9,11]. From the results, we can see that several African countries have also published a significant number of ST publications. However, their contribution was lesser compared to other countries, which could be attributed to a limited number of resources and funds to support publication fees in highquality journals or databases.
In our study, coauthorship analysis was utilized to evaluate the cooperation between different institutions and authors. Results with higher total link strength indicate a greater degree of collaboration among institutions and authors in publishing and carrying out the ST research.
In addition, the keyword analysis highlighted the dominance of ST topics with keywords such as "human," "male," "female," "middle-aged," and "children," among others. This gives vital information about the dynamics of the disease as well as the broader scope of ST research. However, key areas

Strength and Limitations
This study is the first bibliometric analysis that evaluates and visualizes the trend of published ST documents from Scopus databases. Nevertheless, the study also has some specific limitations. We restricted our search to Scopus databases, and we did not compare our findings with other scientific databases such as Web of Science (WoS), Embase, Cochrane Library, PubMed, and Google Scholar, which could help provide a better overview of the ST-related published literature.

Conclusion
Our bibliometric analysis provides historical insights and perspectives of ST research during the past 75 years. Korea, India, and China were identified as the major contributors and play leading roles in the global ST research production. The American Journal of Tropical Medicine and Hygiene published the most significant number of articles on ST. Papers from the USA, India, Thailand, and Korea are most likely to have high citation scores. However, the study highlights a need for more focus and research on vaccine development to address this public health issue. Neverthe-less, our findings may help to inspire future works in ST research and specifically encourage stakeholders, researchers, and institutions to focus on the identified hotspot fields.

Data Availability
The data used to support the findings of this study are included within the article.   BioMed Research International