Abstract
Transmission levels and severity of infections in Aedes aegypti-transmitted diseases have been currently intensified. This short communication is a bibliometric approach about research on this vector, which is responsible for more than 25,000 deaths annually. Current scientific research on A. aegypti is characterized, using Scopus as data source. A total of 5039 published articles during the period 2006–2015 were retrieved. Two time-slices to calculate growth rates by countries and subject areas were developed. Co-word analysis for research fronts identification was used. Scientific output was mainly concentrated in four Scopus subject areas: Medicine; Immunology and Microbiology; Agricultural and Biological Sciences; and Biochemistry, Genetics and Molecular Biology. Highest growth rate was observed in Pharmacology, Toxicology and Pharmaceutics. United States, Brazil and India were the most productive countries. Four research fronts were identified: epidemiology; gene expression and biological control; larvicidal and insecticidal effects; and reproduction and insecticide resistance. Literature on A. aegypti during the last 10 years showed an exponential growth. This growing was associated with the identification of mosquitos in new environments, as well as the appearance of outbreaks related to diseases transmitted by this vector.
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Introduction
Aedes aegypti is responsible for 50 million infections and more than 25,000 deaths annually, according to the World Health Organization (WHO). Despite national and regional efforts to control transmission, global distribution of dengue fever involves more geographic areas (including Europe and North America), and many endemic zones show an increase of the intensity of transmission and the severity of infections (Tapia-Conyer et al. 2012; Wilson and Chen 2015).
On the other hand, the re-emergence of yellow fever in Africa and South America (Mascheretti et al. 2013; Soghaier et al. 2013; Staples et al. 2014), the global spread of Chikungunya virus since 2013 (Vega-Rua et al. 2015; Weaver and Lecuit 2015), the appearance and rapid spread of Zika virus in Asia and South America (Musso et al. 2014; Nhan and Musso 2015), and the clear implication of A. aegypti in outbreaks produced by all these viruses, are evidence of a significant and escalating world public health problem.
This brief communication analyzes the published literature on this vector during the 10 years from 2006–2015, from a scientometric perspective. The aim is to reveal the immediate impact of the current alarming situation on research policies around the world, and to identify the main research areas.
Materials and methods
Scopus, developed by Elsevier in 2004, was used as data source. The choice of Scopus takes into account the wide biomedical coverage of this online commercial abstract and citation database, which includes all articles abstracted in the United States National Library of Medicine’s Medline (Reidpath et al. 2011).
A search strategy based on the identification of term “Aedes aegypti” in Abstract, Titles and Keywords was performed. The world scientific output developed during the period 2006–2015 (5039 documents) was selected and retrieved on April 25th, 2016. EndNote X7, developed by Thomson Reuters, was used to create an ad hoc database. The global search strategy was combined with the use of terms “Dengue”, “Yellow Fever”, “Chikungunya” and “Zika”, in order to analyze the behavior of diseases transmitted by the mosquito.
The sample was divided into two time periods (2006–2010 and 2011–2015) with the aim to analyze the behavior of scientific output by Scopus Subject Areas and countries. Using techniques of word co-occurrence analysis, the network of the 200 most frequent terms appearing in the title of articles was visualized. Clustering and mapping techniques, based on the VOS (Visualization of Science) algorithm developed by researchers from Leiden University (Waltman et al. 2010), were used to visualize the main research fronts.
Results and discussion
Literature on A. aegypti in Elsevier’s database showed an exponential growth during the 10-year period, and doubled between 2006 and 2015. The same behavior is observed if we analyze the diseases associated to the studied vector (Fig. 1).
High annual percentage growth rates in each of the diseases transmitted by the mosquito were found. Particularly, scientific output on the vector and their link with Dengue (GR = 12.2%), Chikungunya (GR = 28.3%) and Zika (GR = 90% during the last 4 years of the study) were remarked. Zika experimented an explosion during the first 3 months of 2016 (not covered by the Figure), with more than 300 published articles. English (94%), Spanish (4.4%) and Portuguese (2.2%) were dominant among the 17 languages identified in the set of articles published during the period.
Journals covered by the domain of Medicine (59.14%), Immunology and Microbiology (33.74%), Agricultural and Biological Sciences (33.65%), and Biochemistry, Genetics and Molecular Biology (24.75%) were the most used research communication channels (Table 1). The most cited articles in these areas were about the genome sequence of A. aegypti, the study of Chikungunya fever outbreaks, and the use of the intracellular bacterium Wolbachia as a powerful mechanism to invade natural vector populations, interfering with pathogen transmission.
However, the highest growth rate was observed in journals covered by the area of Pharmacology, Toxicology and Pharmaceutics (GR = 224.8%). The emergence of insecticide resistance has limited the number of active compounds that are used against mosquitoes, which demands the development of new methods and natural products derived from plants to achieve better larvicidal effects.
Time slices were also used to analyze the scientific output behavior by country (Table 2). USA (31.5%), Brazil (13.9%) and India (13.0%) were the most productive countries. Output from Brazil and India are strongly related to the incidence of Dengue fever. Dengue in Brazil has represented up to 60% of the world-wide cases (Fares et al. 2015). In India, it has become a major public health problem in urban areas, and is gradually spreading to rural areas (Sharma et al. 2014).
Cuba is one of the 14 countries that produced more than one hundred papers, but is the only one with a negative growth rate during the period. Nevertheless, there are countries with an increasing research activity during the last 5 years of the period: Saudi Arabia (GR = 637.5%), Pakistan (GR = 487.5%), Italy (GR = 190.5%), The Netherlands (GR = 154.5%), Colombia (GR = 153.6%), China (GR = 143.9%), Singapore (GR = 133.3%), and Mexico (GR = 120.3%). In almost all cases, researches have been compelled by the vector detection in the environment, or the appearance of Dengue and Chikungunya fever outbreaks (Aziz et al. 2014; Brown et al. 2011; dos Santos et al. 2014; Lu et al. 2014; Ooi 2015; Oon and Ng 2014; Sanchez-Casas et al. 2013; Shahzad et al. 2010; Tomasello and Schlagenhauf 2013).
A global approach to research on A. aegypti was observed in Fig. 2. Using techniques of word co-occurrence analysis, based on the network of the 200 most frequent terms appearing in the title of articles, four major research fronts were identified: (a) epidemiology; (b) gene expression and biological control; (c) larvicidal and insecticidal effects; and (d) reproduction and insecticide resistance.
The emergence of Dengue as the most important arboviral disease of humans, the reemergence of yellow fever, and the emergence of Chikungunya and Zika were several topics related to cluster a. In this context, ineffective social policies, extreme growth of urban populations, migration flows, climate changes, poor sanitation, poverty, and lack of financial resources were factors strongly associated with the spread of these infectious diseases.
New chemical products against mosquitos were covered by cluster c; these have been a classic approach during more than 50 years. On the other hand, emerging research trends were covered by cluster b and d. In this sense, the use of A. aegypti in a sterile insect control program using genetic engineering (Winskill et al. 2015), and the transinfection of mosquitos with the bacteria Wolbachia, were promising biocontrol methods during the analyzed period (Iturbe-Ormaetxe et al. 2011). However, research on vaccines and the development of an integrated approach incorporating vector management, environmental solutions and social policies, are vital tools in the fight against Dengue, Yellow Fever, Chikungunya and Zika.
Discussion and conclusion
The bibliometric approach has been frequently used by researchers from biomedical fields. Neglected infectious diseases have received the attention of multiple authors, especially during the last 5 years (Albuquerque et al. 2017; Bundschuh et al. 2013; Vera-Polania et al. 2015; Zyoud 2016). Most of them explore textual and bibliometric facets through the analysis of published papers covered by international databases, using periods of five, ten or even more than 20 years, in order to reveal the state of the art on these diseases.
Results obtained in the current paper confirm a trend observed by several bibliometric studies. It is clear that the increasing growth of research on A. aegypti is strongly related to the wide spread of infectious diseases related to this vector. The Palestinian researcher Sa’ed H. Zyoud observed that number of published documents in the field of Dengue climbed from less than 50 per year before the 1990s to almost 2500 per year in 2015 (Zyoud 2016). A similar behavior is observed by Colombian researchers in the scientific output on Chikungunya virus from 2005 to 2014 (Vera-Polania et al. 2015), and also by Matthias Bundschuh and colleagues (from Germany) in yellow fever research (Bundschuh et al. 2013), and by Priscilla Alburquerque and colleagues (from Brazil) in Zika research (Albuquerque et al. 2017).
The case of Zika is more than alarming. Brazilian researchers observed the relevance of Zika outbreak for public health around the world. They revealed a dramatic increase of scientific publications on Zika from January 2014 to August 2016, using Web of Science, Scopus, Google Scholar and patent databases as data sources. After a manual classification method, they suggested that scientific activity was still focused on basic research, and patent development was concentrated on drug discovery, diagnosis and vaccine development. The association of Zika with microcephaly and other neurological disorders, recently declared by the World Health Organization, is a critical factor behind the growth of scientific output, according to these authors (Albuquerque et al. 2017).
The study of growth rates in our paper demonstrated this increasing research activity. The negative trend for Cuba is probably related to a lower incidence of the Dengue virus during the last 5 years, taking into account that Dengue spread and outbreaks mainly affected Cuban population during the beginning of the present century (Arencibia-Jorge et al. 2008). However, the focus on vector and the use of mapping techniques allow us to identify relevant research areas related to vector control and management. Researchers associated to these areas consider that environmental solutions and social policies would be more effective in a short term during the battle against emerging arboviral diseases.
Transmission levels and severity of infections in A. aegypti-transmitted diseases during the last 10 years had a clear impact on research policies around the world, which was demonstrated by the increasing growth of literature on this dangerous vector in Elsevier’s database. Taking into account that more than half of humanity is living in risk areas, sharing the space with large mosquito populations (Gubler 2011), the battle against viruses’ survival, and their periodic generation of epidemic strains, could be long and hard, and it is still a challenge for physicians and researchers.
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Acknowledgements
This research was partially supported by the Proyecto CITMA-CONACyT (B330.166) and the Empresa de Tecnologías Inteligentes y Modelación de Sistemas S.A. de C.V.
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Vega-Almeida, R.L., Carrillo-Calvet, H. & Arencibia-Jorge, R. Diseases and vector: a 10 years view of scientific literature on Aedes aegypti. Scientometrics 115, 1627–1634 (2018). https://doi.org/10.1007/s11192-018-2650-9
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DOI: https://doi.org/10.1007/s11192-018-2650-9