Global research trends of World Health Organization’s top eight emerging pathogens

On December 8^th, 2015, World Health Organization (WHO) led a meeting of experts and health consultants in Geneva to discuss and publish a priority list of pathogens likely to cause serious outbreaks in the near future bearing in mind that the suggested pathogens had limited or no available effective therapies or preventive measures [1]. The meeting came up with a list of top eight emerging serious pathogens that are of great harmful health consequences. According to WHO, the list is not an ultimate one and is supposed to be reviewed annually to include any new emerging pathogens. The WHO list aims to lay the basis and background for national and international health planning to combat and control any potential outbreaks of these pathogens. Furthermore, the WHO wanted countries, researchers, clinicians, and policy makers to talk about these pathogens and corresponding infectious diseases as part of global awareness and preventive policies which might include developing new and inexpensive diagnostics, therapies, vaccines, and behavioral health measures.

According to WHO, the list of pathogens, which required urgent attention for research and development pertaining to preparedness, included “Crimean Congo haemorrhagic fever, Ebola virus, Marburg, Lassa fever, Middle East respiratory syndrome (MERS) and Severe acute respiratory syndrome (SARS) coronavirus diseases, Nipah, and Rift Valley fever” [1]. These infectious diseases are caused by viruses and some of them, such as Crimean-Congo and Ebola, are associated with high fatality rate [2‐8]. Marburg virus is transmitted to people from fruit bats and spreads among humans through human-to-human transmission [9‐13] while Lassa fever is transmitted to humans through food contaminated with rodent feces or urine [14, 15]. Middle East respiratory syndrome is caused by a coronavirus that was first identified in Saudi Arabia in 2012 [16‐18] while SARS, another coronavirus respiratory disease, was recognized on February 2003 [19, 20]. Nipah virus, identified in 1998, is emerging zoonosis that affects both animals and humans [13, 21‐24]. Rift Valley fever is a viral zoonosis that was first identified among sheep on a farm in the Rift Valley of Kenya [25‐29]. The WHO committee listed another three pathogens/infectious diseases and considered them as serious and require an action as soon as possible. These three serious diseases include Chikungunya, severe fever with thrombocytopenia syndrome, and Zika.

Literature review using Pubmed, Google Scholar and Scopus showed that bibliometric studies on SARS or Ebola or Nipah virus have been carried out, but as a single disease and not as a group of diseases with potential future severe epidemics [25‐29]. The collective analysis of literature on top eight pathogens will give a more comprehensive view on these infectious diseases and will help identify which one needs to be given top priority for funding and research.

It has been reported that mapping literature with certain statistical methods could help in detection of emerging infectious disease outbreaks particularly in the presence of internet with thousands of reports being easily communicated among public health specialists and healthcare providers [30, 31]. Based on all of the above, we carried out this bibliometric study to analyze literature on top eight emerging pathogens suggested by WHO. Specifically, information regarding number of publications over time, contribution of various countries, international collaboration, active authors and institutions, journals that are actively publishing articles, citations analysis, geographical distribution of publications, visualization of inter-country collaboration, and top cited articles will be presented. This kind of analysis will be of value to virologists, pharmacist, medicinal chemist, and clinicians who are interested in infectious viral diseases and in developing effective preventive and curative pharmaceutical products. Young researchers need to direct their research efforts toward emerging diseases because they are considered top priority and a bulk of financial support will be invested in these diseases. Healthcare workers in the field of travel medicine need to be aware of the map of infectious diseases that quickly cross borders from one country to another leading to spread of diseases with potential negative impact on public health and tourism industry.

For this study, Scopus search engine was chosen to retrieve required literature. Scopus was used because of its advantages over other databases such as Web of Science (WoS), Google scholar or Pubmed [32]. According to Falagas et al. study, no database is perfect and each has certain merits over the other. For example, PubMed and Google Scholar are free to use in contrast to Scopus and WoS. PubMed lacks citation analysis in contrast to other databases. Scopus offers about 20% more coverage than Web of Science and 100% of Medline database is covered by Scopus. Google Scholar is the largest in terms of coverage but results obtained by Google Scholar have inconsistent accuracy. Although Scopus covers a wider journal range, it is currently limited to articles published after 1995 when compared with WoS [32]. In the current study, we preferred the use of Scopus because of its wider coverage since we are interested in global research activity in the eight emerging pathogens. Many of the journals published from developing countries, where these infectious diseases were found, are indexed in Scopus. This is reflected in the number of journals covered by Scopus versus those covered by WoS [32].

In the current study, keywords used were the names of diseases that appeared in the WHO top eight list. To avoid errors, the names of diseases were followed by conditional keywords such as “virus OR viral OR fever OR hemorrhagic OR haemorrhagic OR corona* OR coronavirus OR infection OR infectious). Fig. 1 illustrates the steps followed along with keywords and search query used in Scopus to retrieve required data.

The data obtained were refined using the side functions in Scopus. Such functions include: 1) time limitation which was set for this study from 1996 to 2015, 2) source type of data which was set in this study to be journal articles while books and book chapters were excluded, and finally 3) type of documents and for the purpose of this study all types of documents were included except errata (correction).

Analysis of data was carried out using the “analyze” function in Scopus menu bar. Analysis included annual number of published documents, productivity of each country, author, preferred journals for publishing research on top eight emerging pathogens, geographical distribution, network visualization, and institution/organization. Scopus allows for citation analysis such as total number of citations, Hirsch index (h-index), and top cited articles. The h-index is a parameter used to measure productivity and scientific impact of an author, institution, or country, or even a subject area [33]. Scopus can also give analysis about active journals in publishing articles on studied diseases. Active journals were presented along with Impact Factor (IF) which was obtained from the Journal Citation Report published by Thomson Reuters.

An important feature in Scopus is that it allows exclusion or limitation which allow researchers to identify articles published by a single author or a single country. Based on this, we divided articles into two types: (1) single country publications (SCP) in which all authors have the same country affiliation and such publications represent an intra-country collaboration, and (2) multiple country publications (MCP) in which authors have different country affiliation and such publications represent inter-country collaboration.

In bibliometric studies, not all data can be presented. In most bibliometric studies, active or most productive countries, authors, institutions/organizations, and journals are usually presented. In this study, with large number of retrieved documents, only countries, authors, institutions, and journals with a minimum productivity of 100 documents were presented and ranked. The cutoff point of 100 publications have been previously used in other bibliometric studies [34]. For analysis pertaining to each infectious disease, only the top 10 productive countries were presented.

An important preventive aspect of most serious infectious diseases is the development of vaccines for prevention of spread. In this study, publications pertaining to vaccine development against any one of the top eight emerging pathogens were sought and presented. The search query used to search for vaccine development was the same search query used to retrieve publications on the top eight pathogens plus the keyword “vaccin*” with an asterisk to retrieve words such as vaccine or vaccination. The complete search query for vaccine data was presented in Fig. 1.

Statistical Package for Social Sciences (SPSS - 21) was used to create graphs pertaining to growth of publications for each disease. Mean ± standard deviation (SD) and median (Q1 – Q3) were used for descriptive statistics. Finally, bibliometric studies do not involve human or animal subjects and therefore, no ethical approval by Institutional Review Board was required.

A total of 8619 journal articles were retrieved. The highest number of published articles was recorded in 2015 while the lowest number of published articles was recorded in 1996. The growth of publications showed a rising trend in 2003 and 2004 and then in 2014 and 2015. Figure 2 shows the annual growth of publications during the study period.

A total of 28 different languages were encountered in retrieved articles. English (n = 7,661; 88.9%) was the most common followed by Chinese (n = 387; 4.5%), French (206; 2.4%), and Russian (n = 131; 1.5%). The majority of retrieved articles were research articles (n = 6,587; 76.4%). Other types of retrieved documents are shown in Table 1.

The majority of articles (n = 5,406; 62.7%) were published in peer reviewed journals in the subject area of “Medicine” while 3075 (35.7%) were published in peer reviewed journals in the subject area of “Immunology and Microbiology”. The subject areas with a minimum of 100 articles are shown in Table 2. Since some journals fit into more than one subject area, the total percentages in Table 2 exceeded 100%.

This study was carried out to assess worldwide research activity on emerging pathogens expected to cause serious fatal outbreaks in the near future. Several bibliometric studies were carried out and published on infectious diseases in general or on a specific disease such as Ebola [36], SARS [37, 38], and Nipah [39, 40]. However, no bibliometric study was carried out on research activity on a group of viruses suspected of potential outbreaks in the near future. These emerging pathogens need to be looked at as one unit since most of them have similar pathogenic and epidemiologic characteristics.

Our study showed that research activity on emerging pathogens showed an uprising peak in 2003 due to the outbreak of SARS at that time, particularly in Asian countries. Another uprising peak of publications was seen in 2014 due to outbreak of Ebola virus and to a lesser extent the outbreak of MERS-CoV. Between the two peaks of SARS and Ebola, there was a high plateau of research activity that is most probably due to the rise in the number of publications about the remaining five diseases.

International collaboration in research on emerging diseases was high possibly due to spread of these viral infectious outbreaks across borders. Furthermore, the relatively high h-index of 173 indicates that research on these diseases is receiving a high number of citations suggestive of importance and large number of readers. A study concluded that the h-index can be used to estimate the potential impact of a pathogen and to rank individual pathogens or types of pathogens [41]. In our study, Ebola and SARS had the highest h-indices which necessitate prioritizing these two pathogens in planning for the future preventive policies. The finding that Professor Feldmann, R. was the most prolific researcher was confirmed by other bibliometric studies [34].

Infectious diseases like acquired immune deficiency syndrome (AIDS), malaria, and tuberculosis are major infectious diseases affecting millions of people and draining billions of US dollars of research funds [42, 43]. Research activity on malaria, tuberculosis, and AIDS have made some success in controlling the spread of such diseases and in developing potent and effective therapies. For example, the discovery of the effective drug artemisinin has greatly changed the therapeutic approach of malaria and enhanced control and eradication of malaria [44‐46]. Actually, the Chinese scientist Tu Youyou, who discovered the drug artemisinin, was awarded Nobel Prize in Medicine in 2015 [47, 48]. In case of the top eight emerging pathogens which are expected to cause serious outbreaks in the near future, no effective therapy is available so far and no preventive measures are being developed to face a sudden worldwide outbreak of these infectious diseases. Calls for strengthening preparedness for Crimean-Congo [49] and MERS-coronavirus [50‐52] have been published. The WHO stated that research remains the cornerstone for reversing trends of serious outbreaks of certain viral diseases and that research will improve methods for surveillance, prevention, and control. Unfortunately, the increased funding for AIDS created a shortage of funding for other infectious diseases [53]. A study that compared research output and citations among three infectious diseases indicated that funding has a positive influence on research output and citations for a particular disease [54].

In most bibliometric studies, the USA, the UK, Germany, and other European countries appeared in the most active list of publications. However, in this study, additional countries in Asia and Africa, and Middle east did appear in the top active list for each disease emphasizing the global threat of such infectious diseases. A bibliometric analysis on infectious diseases reported that USA ranked as top productive country but China is increasing its place among the top five countries [55]. Actually, many countries start to focus their research efforts on infectious diseases as a national health burden [56]. The participation of Asian, African, and Middle eastern countries in research activity pertaining to top eight emerging infectious diseases was clear and prominent. Outbreaks of emerging viral infectious diseases have been commonly reported from many countries in Africa, Asia, and Africa [52, 57‐62]. For example, MERS-CoV and Crimean-Congo fever have been reported in more than 20 countries, mostly in Asia, Africa, and Middle East [63‐77]. The outbreaks of SARS in Hong Kong and China had a great economic and public health impact [78‐80]. Many of these infectious diseases were initially reported in Africa, such as Ebola, Lassa fever, and Rift valley fever [81‐86]. The Marburg virus was initially reported in Germany and spread to other neighboring countries and that is why China and Hong Kong did not show in the top productive countries on Marburg disease.

Our study has few limitations that need to be stated. Scopus is a large and comprehensive database but not all journals are indexed in Scopus and therefore, some articles about the studied diseases published in un-indexed journals might be missed. Furthermore, the keywords used might not be 100% accurate although the validity of the search query was tested by manual review of 10% of retrieved articles, false positive and false negative results remain a possibility. The ranking of countries and institutions based on citations did not take into account self-citations which affects the validity of results. These limitations and others are found in most bibliometric studies [71, 87‐91]. This study focused only on the top eight emerging infectious diseases expected to cause severe outbreaks in the near future. However, the other three serious infectious diseases which in include Zaika were not included in the analysis. Finally, we should always bear in mind that no database is perfect and even might have some bias by over-representing journals with English language. Therefore, bibliometric results should always be considered with caution [92].

The number of publications on diseases expected to cause severe outbreaks in the near future showed two clear peaks in the past two decades; one for SARS and one for Ebola. The clear increase in number of publication on the studied diseases during relatively short period of time is an indication of how science and health information flows rapidly across borders to create similar concerns among different countries. Bibliometric methods can be used to prioritize efforts and direct research funds to help control emerging diseases [41]. Although the USA is leading the research on these diseases, the share of Asian, African, and Middle Eastern countries was apparent. International collaboration in research on these diseases was relatively high for most countries. Search for an effective vaccine was clearly strong for Ebola and SARS.