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Chikungunya virus (CHIKV) is a mosquito-borne alphavirus belonging to the family Togaviridae (), named after the debilitating fever and severe arthralgia it causes (). The virus was first identified in 1952 during an outbreak in Tanzania, Africa (). For decades, CHIKV remained endemic primarily in parts of Africa and Asia. However, in 2004, a key mutation (A226V) in the E1 gene of the virus emerged on the coast of Kenya, enhancing its adaptability to mosquito vectors and facilitating more efficient transmission (). This genetic change triggered an unprecedented global resurgence, spreading rapidly from Indian Ocean islands to Southeast Asia, the Americas, and some temperate regions of Europe. To date, CHIKV has been reported in over 100 countries and territories, causing approximately one million infections annually worldwide, posing a significant and ongoing public health challenge on a global scale ().

The epidemiological situation of CHIKV is complex and continually changing. Global warming has expanded the habitat range of Aedes spp. vectors, such as Aedes aegypti and Aedes albopictus . These vectors possess strong ecological plasticity, exhibit opportunistic feeding behavior, and demonstrate high flexibility in utilizing both urban and natural breeding sites. These characteristics facilitate their widespread dispersal and successful adaptation across tropical, subtropical, and even temperate regions (). In addition, frequent international travel and trade have accelerated the long-distance spread of the virus, resulting in highly unpredictable outbreaks and extensive geographical distribution (). Compounding the challenge, a considerable proportion of patients progress from acute infection to chronic and disabling arthritis, with symptoms that can persist for months or even years. This leads to significant workforce loss, reduced quality of life, and imposes a substantial economic disease burden on society ().

In terms of pathogenesis, CHIKV infection directly causes viremia and cytopathic effects, and triggers a strong host immune-inflammatory response. The virus enters the human body through the bite of an infected Aedes mosquito, invading the skin and relying on the E2 glycoprotein to bind host cell glycosaminoglycans (GAGs) and the MXRA8 receptor for cellular entry (; ; ). Viral RNA is translated into non-structural proteins (nsPs), and subgenomic RNA is further translated into structural proteins that govern viral assembly and release (). The inflammatory response induced by the virus is often accompanied by elevated levels of immune mediators and the infiltration of immune cells into infected joints and surrounding tissues (). Fatal outcomes due to CHIKV are associated with increased levels of pro-inflammatory cytokines and chemokines (). The specific mechanisms underlying acute and chronic arthropathic damage, particularly the relationship between viral persistence and autoimmune responses, remain major focuses and challenges in current research.

Currently, there are no FDA approved drugs for the treatment of CHIKV infection, and alternative therapeutic options against this viral disease remain limited. Research indicates that developing drugs targeting proteins encoded by the CHIKV genome, including non-structural proteins nsP1 to nsP4 and structural proteins such as E3, E2, E1, C, and 6 K, represents a promising strategy to improve treatment efficacy and reduce mortality in CHIKF (). Targeted disruption of nsP3 assembly has been shown to significantly inhibit viral replication and transcription (). Studies by have identified natural compounds such as chloroquine, apigenin, and chrysin as exhibiting antiviral activity against CHIKV (). During the viremic phase, the use of anti-CHIKV monoclonal antibodies has successfully reduced the spread of the virus to distal joints and tissues (; ). The long non-coding RNA ALPHA (prohibiting human alphaviruses) interacts with the CHIKV genomic RNA and specifically targets viral RNA replication (). Although researchers have developed various vaccine candidates, including live attenuated vaccines, virus-like particle vaccines, and mRNA vaccines, which show promising immunogenicity (; ; ), the unpredictable geographic spread of outbreaks and the genetic diversity of the virus pose major challenges for Phase III efficacy trials and broad applicability. Numerous questions remain regarding vaccine safety and immunogenicity in children, pregnant women, and immunocompromised populations, as well as how vaccine coverage may alter population level immunity and transmission patterns of alphaviruses ().

This study aims to systematically sort out the molecular biological features and epidemiological evolution trends of CHIKV using bibliometrics, conduct an in-depth exploration of its immunological and virological mechanisms of pathogenesis, and comprehensively review the latest progress and existing obstacles in the field of current antiviral drug and vaccine research and development. By synthesizing current scientific evidence, we seek to offer valuable insights to guide future basic research on CHIKV and inform the design of therapeutic and preventive strategies, ultimately contributing to the effective control of this significant emerging infectious disease.

The literature search for this study was conducted using the Web of Science Core Collection (WoSCC) database. This database was selected as the sole source for three primary reasons: First, its rigorous journal selection process ensures the inclusion of high-quality, influential literature, which forms a reliable core dataset for analysis. Second, WoS provides standardized and complete citation data, which is crucial for the accuracy of co-citation and collaboration network analyses. Third, using WoS ensures methodological consistency and comparability with the vast majority of existing bibliometric studies. The retrieval was performed on August 6, 2025, using the Topic (TS) field with the following query: TS = (‘CHIKV’ OR ‘Chikungunya virus’ OR ‘Chikungunya fever’ OR ‘CHIK’). Articles published between January 1, 2015, and December 31, 2024, were included, yielding an initial result of 5,625 publications. A 10-year time span was selected to ensure both the timeliness of research trends and the representativeness of the data. This duration is widely recognized in bibliometric studies as suitable for capturing emerging research directions while maintaining consistency and analytical depth. To ensure data integrity and reproducibility, the search was completed within a single day, and only English-language original research articles and reviews were considered. Two researchers independently screened the literature. Records unrelated to CHIKV research were excluded, along with non-qualifying publication types such as conference abstracts, case reports, letters, and preprints. A total of 3,709 eligible publications were ultimately included. The detailed screening process is illustrated in .

To examine the development, evolutionary trends, and emerging research fronts in CHIKV studies over the past decade, this study employed VOSviewer (version 1.6.20), CiteSpace (version 6.4.R1), and the online platform https://bibliometric.com/application . The analysis covered multiple dimensions, including institutional and journal distributions, country/region contributions, author collaborations, keyword clustering, and characteristics of highly cited references.

CiteSpace (version 6.4.R1) was used to visualize the analysis of scientific literature, citation counts, total publications, key disciplines and journals, research institutions and collaborations, as well as author analyses. The software also supports keyword frequency analysis, keyword clustering, and burst detection. The time span (2015–2024) was divided into 1-year slices. For each slice, the top 50 cited references or occurring keywords were selected. The resulting networks were pruned using the Pathfinder algorithm. In co-occurrence maps generated by CiteSpace, node size corresponds to the number of publications, connections between nodes represent collaborations, and line thickness reflects the frequency of cooperation—more connections and thicker lines indicate stronger co-citation or co-occurrence relationships. Furthermore, the knowledge structure of a field can be visualized through cited references, where highly cited works are regarded as classic and authoritative. In the citation network, node size is proportional to co-citation frequency, and links between nodes indicate co-citation relationships. Overall, CiteSpace provides an intuitive representation of core authors and keyword networks within a specific research domain.

VOSviewer (version 1.6.20) was also extensively applied in the analysis and visualization of scientific literature, keywords, author relationships, as well as conducting co-occurrence analysis, network visualization, heat maps, and cluster analysis. VOSviewer was configured with the following thresholds: a minimum occurrence of 47 for keyword co-occurrence analysis, a minimum citation count of 90 for reference co-citation analysis, and inclusion of the top 30 countries for international collaboration mapping. In its co-citation maps, nodes represent individual units (e.g., publications, keywords, or authors), and nodes of the same color belong to a related cluster. Node diameter corresponds to the number of publications or citations, with larger nodes indicating key research themes. The distance between nodes reflects the strength of their relationship—shorter distances imply stronger associations. In this study, VOSviewer was used to generate country/agency distribution maps, international collaboration networks, and visualizations of keywords and co-cited references. Additionally, Microsoft Office Excel 2021 was employed for organizing and statistically describing publication-related metrics.

Based on the keyword search, a total of 5,625 publications were initially identified. Following screening by publication year, document type, and language, 3,709 research articles and reviews published in the last decade (2015–2024) were ultimately selected from the Science Citation Index Expanded (SCI-Expanded) edition of the Web of Science Core Collection. These publications have accumulated 13,028 total citations, with an average of 3.51 citations per article. The H-index for the entire dataset was 29. The detailed screening process is presented in .

The annual number of publications increased from 273 in 2015 to 326 in 2024, demonstrating a modest overall upward trend over the past decade. The number of CHIKV related publications peaked at 441 in 2020 (). This irregular trend may be indirectly attributed to the COVID-19 pandemic, which stimulated research output in areas such as COVID-19 and CHIKV co-infections, differences in clinical manifestations, diagnostic approaches, and potential immune interference.

Analysis at the country/region level indicates that the 3,709 publications originated from 163 countries or regions. Among the top 10 countries/regions in terms of annual publication output in CHIKV research between 2015 and 2024, the U.S. led with the highest number of publications, totaling 1,266 (34.13%), followed by Brazil with 641 (17.28%) and India with 432 (11.65%). Publications from the U.S. accumulated 35,464 citations, accounting for 32.93% of the total citations. Those from Brazil received 15,891 citations (14.76%), while Indian publications were cited 6,794 times (6.31%). The U.S. also achieved the highest H-index of 86, significantly exceeding that of other countries/regions. Singapore recorded the highest average citations per article at 50.88, although its total publication output and H-index were relatively lower compared to the U.S. ( and ).

Efficient collaboration among institutions and countries is crucial for fostering academic exchange and advancing scientific research. presents the collaboration network among the top 30 countries/regions with the highest publication output in the field of Chikungunya virus from 2015 to 2024. The U.S. and China emerged as the two leading contributors, with collaboration intensity substantially surpassing that of other nations. Additionally, the U.S. maintained strong collaborative ties with Brazil, Sweden, Colombia, China, and South Korea, while Australia engaged in extensive partnerships with the U.S., the U.K., France, Brazil, India, and China, among others. illustrates the total link strength and the number of collaborative links (“Documents” metric) for the top 30 most productive countries, revealing distinct collaboration profiles. The U.S. demonstrates the highest total link strength (985), far exceeding that of Brazil (336) and India (170), underscoring its central and highly integrated role in the global research network. Conversely, Brazil leads in the number of collaborative links (2,990) but exhibits a comparatively moderate total link strength (336). This discrepancy suggests that Brazil’s numerous international collaborations may translate into less cohesive integration within the broader network compared to the U.S.

Among the top 10 institutions with the highest number of publications (NPs) in the field of CHIKV research, Fundação Oswaldo Cruz from Brazil ranked first with 237 publications, followed by Université Paris Cité (191 publications) and the Pasteur Network (184 publications) from France (). Excluding the Pasteur Network, French institutions accounted for five of the top 10 positions, while the U.S. and Brazil each contributed two institutions, highlighting the strong research capacity and high academic standard of French institutions in Chikungunya virus studies. Furthermore, we analyzed collaborative relationships among these research institutions (). The results revealed that Institut Pasteur maintains close collaborations with Aix-Marseille University, University of Oxford, Emory University, Mahidol University, and Université de Montpellier. Similarly, Universidade Federal de Minas Gerais demonstrated strong collaborative ties with Universidade de São Paulo, Fundação Oswaldo Cruz, Universidade Federal da Bahia, Universidade Federal do Rio de Janeiro, Universidade Federal de Pernambuco, and Yale University.

The top 10 most prolific authors in the field of CHIKV research contributed a total of 468 publications, accounting for 12.6% of the total output over the past decade. Scott C Weaver from the University of Texas Medical Branch at Galveston ranked first with 75 publications, followed by Andres Merits from the University of Tartu (71 publications) and Lisa F.P. Ng from the Agency for Science, Technology and Research (54 publications). Notably, Scott C Weaver also led in total citations (NC = 3,657) and H-index (), while ranking second in average citations per article (51.12), reflecting the broad recognition of his research among peers (). Furthermore, these top 10 authors are affiliated with institutions across seven different countries/regions, indicating a globally distributed research effort dedicated to the study of CHIKV.

Among the top 10 journals that published the most CHIKV research over the past decade, PLOS Neglected Tropical Diseases ranked first with 258 publications (2024 Impact Factor: IF 3.4), followed by Viruses (Basel) with 220 articles (IF 3.5) and the Journal of Virology with 111 articles (IF 3.8) (). PLOS Neglected Tropical Diseases specializes in publishing groundbreaking research in the field of neglected tropical diseases. Its dedicated section, “Virus,” focuses on studies related to arboviruses, zoonotic viruses, and other emerging and re-emerging viral infectious diseases, with particular emphasis on the transmission mechanisms, control strategies, and innovative therapies for viruses such as dengue and chikungunya in resource-limited settings. Among the top 10 journals, the majority had an Impact Factor higher than 3.000. Approximately 29.60% of CHIKV related publications (1,098 out of 3,709) were published in these top 10 journals.

The citation count of individual articles reflects hotspots and trends in CHIKV research. lists the top 10 most cited papers in this field, and illustrates the annual variation in GCS for these 10 highly influential publications. The most cited article (1,353 citations) was published by Kraemer, Moritz U.G. et al. in 2016 in New England Journal of Medicine (IF 78.5). The team conducted a follow-up study in Rio de Janeiro on Zika virus infection in pregnant women, systematically described maternal clinical symptoms and the impact of acute Zika virus infection on infants (). The second article (1,352 citations) was published by Kraemer, M.U.G. et al. in 2015 in eLife , systematically assessed the global distribution of Aedes aegypti and Aedes albopictus , the primary vectors for arboviruses such as dengue and chikungunya. By integrating the largest contemporary database for both species and analyzing relevant environmental variables, the study predicted their global distribution and provided a basis for defining the current spatial boundaries of local transmission of dengue and chikungunya viruses (). Ranking sixth was a study by Dejnirattisai, W. et al. published in Nature Reviews Immunology in 2016. The study found that plasma from individuals immune to dengue virus (DENV) exhibited cross reactivity with ZIKV and could mediate antibody-dependent enhancement of ZIKV infection, providing basis for understanding pathogenesis and informing future vaccine for both ZIKV and DENV (). In addition, other highly cited articles focused on Zika virus detection, sequencing, and phylogenetic evolution (; ; ), overviews of the epidemiology, diagnosis, and treatment of CHIKV and dengue viruses (; ) and the susceptibility of Aedes aegypti and Aedes albopictus to viruses and their resistance to insecticides (; ).

Among the top 10 most productive research areas related to Chikungunya virus, the categories with the highest number of publications were: Infectious Diseases (793 articles), Virology (730 articles), Tropical Medicine (669 articles), Parasitology (567 articles), Microbiology (458 articles), Public Environmental Occupational Health (353 articles), Immunology (338 articles), Science Technology Other Topics (304 articles), Biochemistry Molecular Biology (261 articles) and Pharmacology Pharmacy (246 articles). Among all research categories, ‘Infectious Diseases’ accounted for the highest proportion, while ‘Pharmacology Pharmacy’ had the lowest proportion ().

The co-occurrence analysis of keywords extracted from the titles and abstracts of 10,158 publications. A total of 111 keywords that appeared more than 47 times were identified and grouped into three clusters (). Cluster 1 (Red, 44 items) focuses on the pathogenic mechanisms and complications of CHIKV. Cluster 2 (Green, 34 items) emphasizes the transmission routes and vector distribution of CHIKV. Cluster 3 (Blue, 33 items) concentrates on epidemiological surveillance and outbreak-related studies of CHIKV. color-codes all keywords by their average publication year (APY) to indicate recency. Apart from ‘epidemiology’ (Cluster 3, APY: 2020.19), which appeared 211 times, the most recent keywords include: ‘arboviruses’ (Cluster 2, APY: 2020.12, 197 occurrences), ‘pathogenesis’ (Cluster 1, APY: 2020.10, 157 occurrences), ‘antiviral activity’ (Cluster 1, APY: 2020.14, 88 occurrences), ‘coinfection’ (Cluster 3, APY: 2020.17, 84 occurrences), ‘immunogenicity’(Cluster 1, APY: 2020.66, 67 occurrences), ‘prevalence’ (Cluster 3, APY: 2020.15, 60 occurrences).

Furthermore, indicates that keywords such as ‘hypervariable domain’, ‘chikungunya virus infection’, ‘ aedes aegypti ’, ‘chikungunya virus vaccine’, ‘different viral epidemic outbreak’, ‘acute encephalitis syndrome’ and ‘promising strategy’ have consistently attracted significant attention in CHIKV research. Among the top 20 keywords with the strongest citation bursts (), “indian ocean,” ‘arthralgia’ and ‘reemergence’ ranked highest in burst strength, while ‘sequence’, ‘double blind’, ‘safety’ and ‘mechanisms’ emerged as new hotspot keywords within the past year. Synthesizing the results from –, it is evident that phylogenetic analysis, pathogenic mechanisms, drug therapy, and vaccine development remain core themes of ongoing interest in CHIKV research.

This study analyzed 3,709 publications through bibliometric mapping and visualization, employing quantitative, qualitative, and integrative research methods to systematically evaluate the research progress, hotspots, and future directions of CHIKV. To our knowledge, this is the first bibliometric study conducted in this research field.

The annual number of publications showed a gradually stabilizing growth pattern, increasing from 273 in 2015 to 326 in 2024, reflecting a modest upward trend over the past decade. This indicates sustained academic interest in CHIKV research and a gradual expansion of research scale. The U.S. ranked first in publication output with 1,266 articles (34.13%), largely attributable to the high productivity of the University of Texas System (137 articles) and the University of Texas Medical Branch (126 articles) in this field. Brazil ranked second with 641 articles (17.28%), followed by India with 432 articles (11.65%). Among the top 10 institutions, French institutions accounted for five, excluding the Pasteur Network, while the U.S. and Brazil each contributed two. Notably, India, despite ranking third in total publication output, had no institutions in the top 10. This suggests that although India has a high overall output, research achievements may be dispersed across numerous universities and research institutes, lacking internationally competitive core flagship institutions. This dispersion may prevent high-quality research from being concentrated in a few leading centers, thereby affecting institutional rankings. Institutions in France and the U.S. generally possess strong international collaboration networks and resource integration capabilities. In contrast, Indian institutions may have relatively weaker participation in international collaborations, joint research projects, or global scientific networks, limiting their international visibility and influence. India’s high number of collaborative documents relative to its total link strength indicates a tendency among Indian research institutions to establish deep and stable partnerships with a limited number of core collaborators, reflecting a relatively limited diversity in its international collaboration network. The U.S. maintained close research exchanges with Brazil, Sweden, Colombia, China, and South Korea, while Australia frequently collaborated with the U.S., the U.K., France, Brazil, India, and China, among others. In terms of institutional collaborations, the Institut Pasteur maintained close relationships with Aix-Marseille University, the University of Oxford, Emory University, Mahidol University, and the Université de Montpellier. Similarly, the Universidade Federal de Minas Gerais collaborated extensively with the Universidade de São Paulo, Fundação Oswaldo Cruz, the Universidade Federal da Bahia, the Universidade Federal do Rio de Janeiro, the Universidade Federal de Pernambuco, and Yale University. Professor Scott C. Weaver published the highest number of related articles (75 papers). His research primarily focuses on the evolution and epidemiology of arboviruses (; ; ; ), pathophysiology and factors contributing to severe CHIKV infection (), mechanisms of mosquito infection and transmission (; ; ), clinical features and complications (; ), treatment strategies (; ), as well as vaccine development and efficacy evaluation (; ; ).

The findings from our bibliometric analysis of countries, institutions, authors, and journals provide valuable insights for designing innovative collaboration models that can enhance cooperative efficiency and drive future advancements in CHIKV research. At the country level, the dominant roles of the U.S., Brazil, and India in publication output, coupled with their distinct collaboration patterns, suggest the need for strategic partnership frameworks. For instance, while the U.S. exhibits broad and intensive international linkages, Brazil and India show deeper but narrower collaborative ties. This indicates an opportunity for hub-and-spoke collaboration models, where highly connected countries (e.g., U.S., France) serve as hubs to facilitate multi-directional knowledge exchange and resource sharing with regionally focused partners. Such models could help diversify the collaboration networks of countries like India and Brazil, enhancing their global research visibility and impact. At the institutional level, the concentration of high-output institutions in France (e.g., Institut Pasteur, Université Paris Cité) and Brazil (e.g., Fundação Oswaldo Cruz) highlights the importance of institutional alliance-building. The close collaborations between French and Brazilian institutions with partners in Europe, North America, and Asia demonstrate the effectiveness of transcontinental research consortia. Future initiatives could formalize these partnerships into structured international research networks focused on specific themes—such as vector biology, vaccine development, or genomic surveillance—enabling shared data platforms, joint funding proposals, and coordinated multi-center trials. Author-level analysis reveals that prolific researchers like Scott C. Weaver often act as collaboration nuclei, bridging multiple institutions and disciplines. Encouraging the formation of theme-based research clusters around such key authors can foster interdisciplinary innovation. For example, integrating virologists, immunologists, epidemiologists, and data scientists within a single collaborative framework could accelerate the translation of basic findings into public health applications. Journal analysis indicates that high-impact journals such as PLOS NEGLECTED TROPICAL DISEASES and VIRUSES BASEL serve as important dissemination channels for CHIKV research. These journals could play a more active role in curating special issues or thematic series that highlight collaborative international studies, thereby incentivizing cross border research partnerships and promoting the integration of diverse datasets and methodologies. To fully unlock the potential of global cooperation, this study proposes exploring the establishment of a CHIKV Research Coordination Platform—a combined digital and organizational infrastructure designed to support real-time data sharing, joint training programs, and coordinated response mechanisms during outbreaks. Such a platform could integrate genomic, epidemiological, and clinical data from multiple countries, thereby facilitating the development of predictive models and equitable vaccine distribution strategies.

According to the cluster analysis in , , recent research hotspots related to CHIKV have primarily focused on phylogenetic analysis and epidemiology, pathogenesis and drug therapy, as well as vaccine development. Research in phylogenetic analysis and epidemiology includes the following representative studies. Krambrich J et al. investigated the evolution and molecular history of the East/Central/South African (ECSA) genotype to determine the origin of the 2018–2019 CHIKV outbreak in Thailand. Through comparative phylogenetic analysis based on complete CHIKV genomes and protein modeling, the team identified specific mutations in the E1/E2 spike complex E1 K211E and E2 V264A which may alter the virus’s vector competence, transmission efficiency, and pathogenicity (). found that although the CHIKV strains circulating in Bangladesh and Thailand from 2017 to 2019 both belonged to the Indian Ocean Lineage (IOL) of the East/Central/South African (ECSA) genotype, they lacked the E1-226 mutation and instead acquired novel mutations at positions E1-211 and E2-264. These changes gave rise to a distinct new sub-lineage, which exhibited enhanced transmissibility by Aedes albopictus (). , through a combination of active surveillance, screening of historical and recent samples, and whole genome sequencing, identified the Asian lineage from the 2016 outbreak and the ECSA lineage from 2023 in Argentina, reflecting the dominance of specific variants in Latin America. A phylogenetic analysis of 205 confirmed CHIKV infection cases during the 2007 outbreak in Italy showed a high similarity between the strains identified in Italy and those from earlier outbreaks in Indian Ocean islands (). systematically described the molecular virology, clinical manifestations, diagnosis, prevalence, genotype distribution, evolutionary relationships, and epidemiology of CHIKV infections in Asian countries over the past 65 years. This comprehensive review provides critical insights for guiding epidemiological studies, improving control and prevention strategies for future CHIKV outbreaks, and supporting the development of novel vaccines and antiviral drugs against CHIKV ().

Research on the pathogenesis of CHIKV, Structural analysis of the crystal structure of nsP2 N-terminal RNA helicase domain (nsP2h) in complex with genomic RNA demonstrated that it engages in stacking interactions with RNA bases via three critical hydrophobic residues (Y161, F164, and F287). The mutation of residue F287 impairs both ATPase activity and RNA-binding capacity, double mutation at Y161 and F164 completely abolishes viral replication (). Both domains and the hinge region of MXRA8—the molecular receptor for arthritogenic alphaviruses—interact with residues of the CHIKV envelope protein E1-E2. The stalk region of MXRA8 was found to be critical for CHIKV viral entry (). Additionally, a single FGDF motif in the CHIKV nsP3 is sufficient to support viral infection and dissemination in mosquitoes, while a double motif is essential for efficient transmission from mosquito saliva to vertebrate hosts. These findings elucidate the molecular mechanisms underlying the alphavirus transmission cycle and provide new insights for the development of intervention strategies against arboviral diseases (). The CHIKV nsP1 forms a crown shaped ring structure through the assembly of 12 copies at 2.38 Å resolution, enabling material exchange between the viral replication complex and host cells ().