A bibliometric analysis of tularemia, endemic for Türkiye

Abstract

Objectives: We conducted a bibliometric analysis study to determine the sufficiency of the national literature on this disease, which is endemic to our country, and to guide future studies.

Materials and methods: The Turk Medline database was scanned in the study. Publications between January 1999 and December 2020 were searched using the keyword “tularemia”. A total of 101 publications were detected. Reviews and case reports were not included in the study. A total of 40 articles and letters to the editor (including study data) were evaluated. Google Scholar and Google Search engine were used to access the full texts of the articles. Because the full text of five articles was unavailable, they were not included in the content analysis. Articles were evaluated in terms of the year of publication, the institution, the location, the number of authors, the keywords, the sampling, sample size, the number of keywords, the study subject, the number of citations, the language of publication, and the journal which it was published. The social network analysis method was also utilized to define the network structure and examine the connections between structures. For this purpose, UCINET and NetDraw programs were used.

Results: A total of 24 provinces participated in the research. The publications were from 31 different institutions, with the majority being from university hospitals (45%) and the Central Anatolia Region (45%). The majority of studies were carried out on patients (40%). The average number of citations was 4.5±1.13. Two articles got more than 20 citations. Most studies (60%) were conducted between 2010 and 2015.

Conclusion: Tularemia is a zoonotic disease with complex epidemiology. Many aspects of this disease are currently unclear. Studies on these subjects are required since the epidemiological role of animal hosts, potential vectors, maintenance mechanisms in different ecosystems, and the transmission routes of the disease need to be better understood.

Introduction

Tularemia is a zoonotic disease caused by Francisella tularensis, and it is characterized by fever and lymphadenopathy. Tularemia is also known as “Francis disease, Ohara’s disease, rabbit fever, deer-fly fever, Siberian ulcer, and meat-cutter’s disease”.[1] F. tularensis is a gramnegative intracellular bacterium. This highly contagious microorganism is regarded as a potential biological threat. People are frequently infected as a result of direct contact with animal reservoirs and tick bites. However, cases of tularemia have been reported following contact with a contaminated environment. In the last decade, there have been sporadic cases and waterborne tularemia outbreak with distinct clinical and epidemiological characteristics all over the world. These infections are also a major public health concern. Contamination with human factors has occurred as a result of F. tularensis-contaminated water consumption, use, and various water activities such as swimming and fishing. Furthermore, mosquitoes are the primary vectors of tularemia in Sweden and Finland due to the infection of mosquito larvae in contaminated water environments. Many new aquatic F. tularensis species have been identified in recent years, and these should be considered in tularemia surveillance and control.[2,3]

Tularemia, which has been on the list of mandatory diseases in our country since 2004, has been added to the list of diseases, i.e. group C diseases, that are required to be sentinel notifications in the application of the National Notifiable Diseases Surveillance System due to an increase in the number of cases and reporting of cases from across our country.[4]

This disease is a zoonosis with complex epidemiology, and the reservoir hosts for this pathogen have yet to be identified. Tularemia has been shown in recent years to have a much broader range of hosts and transmission routes than previously thought.[5] This disease, which can cause outbreaks across the world, has remained a major concern in recent years. The disease is considered endemic in countries such as the former Soviet Union, Tunisia, Iran, Canada, Mexico, Türkiye, Israel, China, and Japan. Even though it is rarely reported in African countries, there is more evidence of an increasing presence in Africa.[6] We conducted a bibliometric analysis to assess the sufficiency of the national literature on this disease, which is also endemic in our country, and to guide future research.

Patients and Methods

In the study, the Turk Medline database (www.turkmedline.net/) was searched using the keyword “tularemia”. Publications between January 1999 and December 2020 (a total of 101) were detected. Reviews and case reports were not included in the study. A total of 40 articles and letters to the editor (including study data) were evaluated.[7-46] Google Scholar and Google Search engine were used to access the full texts of the articles. Because the full text of five articles was unavailable, they were not included in the content analysis. Articles were evaluated in terms of the year of publication, the institution, the location, the number of authors, the keywords, the sampling, sample size, the number of keywords, the study subject, the number of citations, the language of publication, and the journal which it was published. The study was conducted in accordance with the principles of the Declaration of Helsinki.

The social network analysis method was also utilized to define the network structure and examine the connections between structures. For this purpose, UCINET 6,718 Windows and NetDraw programs were used. To analyze data, a free version of the program was downloaded from the “https://sites.google.com/site/ ucinetsoftware/home” site. This program is a software package for the analysis of social network data that was created by Lin Freeman, Martin Everett, and Steve Borgatti. It comes with the NetDraw network visualization tool.

Results

In the study, 35 articles with full text were subjected to content analysis and general evaluation, while five articles without a full text were subjected to general evaluation only.

The number of authors ranged from two to 13, with up to four (22.5%) authors. The average number of pages was 6.575±1.75. A total of 24 provinces participated in the research. The publications were from 31 different institutions, with the majority being from university hospitals (45%) and the Central Anatolia Region (45%). The majority of studies were carried out on patients (40%). The majority of articles on the subject were published in the Bulletin of Microbiology and the KLIMIK Journal. It was found to be the first publication in 1999. The most of studies (60%) were conducted between January 2010 and December 2015 (Table 1).

Table 1. Journals in which articles are published

The sample size ranged from 6 to 1,503. Only five studies included a control group, and the average resources were 20±2.52. The average number of keywords was 4.11±1.29, and the number of citations was 4.5±1.13. There were over 20 citations for the two articles (Table 2).

Table 2. General characteristics of the articles (n=40)

When the journals in which the cited articles were published were examined, it was found that there were citations to articles published in nine journals, with the most citation heading to the Bulletin of Microbiology (40.1%) and the KLIMIK Journal (18%) (Table 3).

Table 3. The journals in which cited articles

Discussion

Overall, between 1992 and 2012, 18,343 cases of human tularemia were reported in the WHO-CISID (World Health OrganizationThe Computerized Information System for Infectious Diseases) and ECDC (European Centre for Disease Prevention and Control) databases. Sweden reported 25% of all reported cases, Finland 22%, Türkiye 13%, and the Czech Republic and Hungary each reported about 9%.[5] The ECDC reported 18 cases of tularemia in the EU (European Union) in 2018 and 441 (358, 81% confirmed) in the EEA (European Economic Area). This report includes data from 12 countries, with Norway and Sweden accounting for 45% of all reported cases, accounting for 0.07 cases per 100,000 overall reporting rate.[47]

Since the first case was reported in Lüleburgaz in 1936, tularemia, which can cause epidemics in our country on occasion, has been reported primarily from the Thrace Region of Türkiye. After 1988, cases from the Marmara Region were reported in and around provinces, such as Çanakkale, Bursa, and Susurluk town, and began to be seen throughout the country.[48] There were notifications from other regions of our country, particularly from the Central Anatolia Region, especially in 2009-2010.[1] Figure 1 presents the distribution of case numbers based on data from our country. Similarly, our study revealed that most articles were published between January 2010 and December 2015, particularly as cases began to emerge across the country and the number of cases increased. Although 45% of the publications examined in our study were from the Central Anatolia Region, there was no publication from the Mediterranean Region alone.

Figure 1. Distribution of tularemia cases in Türkiye by year (2008-2017).[49]

Tularemia can affect people of all ages, however, it is less common in children. The number of reported child cases has risen dramatically in recent years, accounting for nearly 10% of all tularemia cases.[1] Our study included three (7.5%) publications that examined child patient groups. These studies were conducted in 2012 and 2013.[22,25,28]

Tularemia is frequently accompanied by nonspecific symptoms, which can cause a delay in diagnosis. In humans, if left untreated, it can lead to serious disease. Sporadic human cases are frequently overlooked, particularly in areas where the disease's prevalence is low.[50] Therefore, clinical findings must be precisely defined. In this context, it was determined that clinical findings and laboratory findings accounted for 40% of all studies.

According to the Türkiye Public Health Agency, there are no tularemia-related mortality reported between 2008 and 2017. According to reports, it causes 0.1-2.88/100,000 morbidities.[1] It was found that there was no research on morbidity and mortality in our study.

In our country, tularemia outbreaks are most common in rural areas, primarily among farming families, housewives, children, hunters, and forest workers.[1] Several publications claim that hunters are at risk for tularemia.[51,52] There were two articles in our study that looked into the presence of tularemia in hunters.[7,32]

F. tularensis holarctica, a less virulent subspecies of F. tularensis, is the most common cause of infection outside of North America.[6] Only one study[35] was found to research on F. tularensis holarctica in our study. This can be interpreted as missing subspecies studies.

In the last 20 years, cases of drinking waterrelated tularemia have been reported in Türkiye, Kosovo, Bulgaria, Georgia, Macedonia, Norway, Sweden, Italy, and Germany. In our country, 28 outbreaks of tularemia and many sporadic cases of tularemia related to contaminated water consumption were reported between 1988 and 2018.[2] This has sparked a global interest in tularemia among researchers. The data on cases of tularemia related to water resources, the existence of Francisella species in aquaculture, and their mechanisms of living in aquaculture were investigated from the British literature in the PubMed database in the Hennebique et al.[2] review study. Only articles from the last two decades (1998-2018) were included It has been reported in this review that outbreaks in Türkiye have a considerable number of cases. According to reports, the oropharyngeal form is the most common, with a similar male-to-female ratio. The review by Hestvik et al.[5] examined cases in humans, pets, and wildlife from 38 European countries between 1992 and 2012, as well as studies on the detection of F. tularensis in arthropod vectors. Searching for F. tularensis holarctica in water samples of F. tularensis subspecies and studies exploring water sources as permanent reservoirs are two environmental studies in Türkiye published in international journals from our country in the medical literature.[53,54] In our research, we found studies on epidemic analysis/retrospective evaluation/ field study,[9,20,34,38,45] investigation of the presence of F. tularensis in stream/mains water,[11] and the search for the existence of F. tularensis in mice using culture, serology, and molecular methods.[21]

In conclusion, tularemia is difficult to understand and hence control the disease with complex epidemiology. Many aspects of this disease are still unidentified. Studies on these issues are needed to gain a better understanding of the epidemiological role of animal hosts, potential vectors, care mechanisms in different ecosystems, and disease transmission.

Cite this article as: Yılmaz M, Alıravcı ID, Uyar C, Dindar Demiray EK, Alkan S. A bibliometric analysis of tularemia, endemic for Türkiye. D J Med Sci 2022;8(3):108-114.

Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.

All authors contributed equally to the article.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

References

1. Tularemi hastalığının kontrolü için saha rehberi. Erişim adresi: http://sbu.saglik.gov.tr/Ekutuphane/ kitaplar/Tularemi%20Saha%20Rehberi.pdf. [Erişim tarihi: 11.12. 2020]
2. Hennebique A, Boisset S, Maurin M. Tularemia as a waterborne disease: A review. Emerg Microbes Infect 2019;8:1027-42.
3. Prokšová M, Bavlovič J, Klimentová J, Pejchal J, Stulík J. Tularemia - zoonosis carrying a potential risk of bioterrorism. Epidemiol Mikrobiol Imunol 2019;68:82-9.
4. Temel Sağlık Hizmetleri Genel Müdürlüğü. Bulaşıcı Hastalıkların İhbarı ve Bildirim Sistemi: Standard Tanı, Sürveyans ve Laboratuvar Rehberi. Ankara: Sağlık Bakanlığı, 2004. Erişim linki: https://www.saglik.gov.tr/TR,11419/bulasici-hastaliklar-ihbari-ve-bildirimisistemi-standart-tani-surveyans-ve-laboratuvar-rehberi. html [Erişim tarihi: 11.12.2020]
5. Hestvik G, Warns-Petit E, Smith LA, Fox NJ, Uhlhorn H, Artois M, et al. The status of tularemia in Europe in a one-health context: A review. Epidemiol Infect 2015;143:2137-60.
6. Penn RL. Epidemiology, microbiology, and pathogenesis of tularemia. Available at: http://www.uptodate.com/ contents/epidemiologymicrobiology-and-pathogenesisof-tularemia?detectedLanguage=en&source=search_ result&search=tularemia&selectedTitle=2%7E55&pro vider=no Provider. [Accessed: 12.12.2020]
7. Bayar Z, Aksu M, Yılmaz M. Elazığ ve çevresinde avcılarda tularemi görülme sıklığının mikroaglütinasyon yöntemiyle araştırılması. Fırat Tıp Dergisi 2018;23:73-7.
8. Bozdağ H. Özekinci T. Tularemia in Diyarbakır province and its surroundings: A rarely known disease. İKSSTD 2020;12:52-6.
9. Köse H, Temoçin F, Sarı T. Tularemi salgını ve sonrası; Mevsimsel değişikliklerin etkisi. Mikrobiyol Bul 2020;54:203-10.
10. Alkan-Çeviker S, Günal Ö, Kılıç SS. Evaluation of tularemia cases in Samsun province between 2011 and 2018. Klimik Derg 2019;32:62-6.
11. Uğur M, Gürcan Ş, Eskiocak M, Karadenizli A. Investigation of tularemia incidence and presence of Francisella tularensis in streams/mains water in a risky region of Thrace. Klimik Derg 2019;32:78-83.
12. Gözdaş HT, Göksel AO. Evaluation of clinical and epidemiological characteristics of tularemia suspected cases in Kastamonu between 2014-2017 years. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 2019;9:45-8.
13. Koçak Ö, Ayan A, Ilıca A, Çakır B, Çekli Y, Kösehan D, et al. Clinical imaging findings of oropharyngeal tularemia: The diagnostic value of iImaging findings. MMJ 2019;6:10-5.
14. Yanık K, Sarıaydın M, Uzun MÖ, Çoban AY, Seçilmiş H. Amasya’da tularemi olgularının mevsimsel ve bölgesel dağılımı. Mikrobiyol Bul 2015;49:139-41.
15. Boz A, Aktuna G, Özgülcü Ş, Sezgin B, Temel F, Çelebi B. Afyonkarahisar ili Dinar ilçesinde 2015 yılı ocak ayında görülen tularemi vakaları. Turk Hij Den Biyol Derg 2016;73:233-44.
16. Korkmaz M, Korkmaz P, Koç F, Gültekin H, Ünlüoğlu İ. Eskişehir ilinde görülen tularemi olgularının değerlendirilmesi. Klimik Dergisi 2013;26:94-7.
17. Karlıdağ T, Keleş E, Kaygusuz İ, Yüksel K, Yalçın Ş. Tularemia: A rare cause of neck mass. Turk Arch Otorhinolaryngol 2015; 53: 19-22.
18. Tahir E, Süslü N, Özer S, Demir Bajin M. Management of cervical lymphadenopathy in patients with tularemia. KBB-Forum 2015;14:10-4.
19. Kader Ç, Erdoğan Y, Günaydın İ, Erbay A. Yozgat ili aile hekimlerinin tularemi konusunda bilgi düzeylerinin değerlendirilmesi. GMJ 2015;26:38-41.
20. Bozkurt İ, Kılıç S. Tularemi Türkiye’nin kuzeyinden güneyine doğru yayılıyor: Kahramanmaraş’da küçük bir salgın. Mikrobiyol Bul 2014;48:413-9.
21. Ünal Yılmaz G, Gürcan Ş, Özkan B, Karadenizli A. Trakya Bölgesi’nde farelerde kültür, seroloji ve moleküler yöntemlerle Francisella Tularensis varlığının aranması. Mikrobiyol Bul 2014;48:213-22.
22. Çelebi B, Kılıç S, Yeşilyurt M, Acar B. Francisella tularensis'in moleküler tanısında yeni geliştirilen kullanıma hazır ticari PCR kitinin etkinliğinin değerlendirilmesi. Mikrobiyol Bul 2014;48:135-42.
23. Çelebi S, Koyuncu E, Elmas Bozdemir Ş, Çetin BŞ, Hacımustafaoğlu MK. Çocuklarda tularemi: Tularemili 15 olgunun klinik, laboratuvar ve tedavi sonuçlarının değerlendirilmesi. Güncel Pediatri 2013;11:57-62.
24. Çelebi B, Kılıç S. Tularemi mikroaglütinasyon testi için tetrazolyum mavisi ile boyalı francisella tularensis antijeninin geliştirilmesi. Mikrobiyol Bul 2013;47:514-22.
25. Ceylan Ö, Köse M, Öztürk MK. Çocukluk çağı tularemi hastalarının değerlendirilmesi. İzmir Dr. Behçet Uz Çocuk Hast. Dergisi 2012;2:131-6.
26. Büyük F, Sahin M, Çelebi Ö, Mor N, Çelebi B. Investigation of Francisella tularensis antibodies in dogs in Kars and Ankara region. Turkish Bulletin of Hygiene and Experimental Biology 2012;69:83-8.
27. Kılıç S, Çelebi B, Bayram Y, Çitil B. Investigation of cross-reactions with Francisella tularensis antibodies to brucella. Turk Hij Den Biyol Derg 2013;70:65-70.
28. Önen S, Paksoy D, Dallar Bilge Y. Çocukluk çağında tularemi olguları. J Pediatr Inf 2012;6:94-100.
29. Dikici N, Ural O, Sümer Ş, Öztürk K, Albayrak Yiğit Ö, et al. Konya bölgesinde tularemi. Mikrobiyol Bul 2012;46:225-35.
30. Koç S, Duygu F,Söğüt E, Gürbüzler L, Eyibilen A, Aladağ İ. Clinical and laboratory findings of tularemia: A retrospective analysis. Kulak Burun Bogaz Ihtis Derg 2012;22:26-31.
31. Balcı E, Borlu A, Öksüzkaya A, Doğanay M. Kayseri’de tularemi ve hekimlerin tularemi konusundaki bilgi ve davranışlarının değerlendirilmesi. STED 2011;20:231-8.
32. Yeşilyurt M, Kılıç S, Çelebi B, Gül S. Tularemi: Avcılar gerçekten bir risk grubu mu? Mikrobiyol Bul 2012;46:153-5.
33. Akıncı E, Ülgen F, Kılıç S, Yılmaz S, Yıldız S, Özdemir B, et al. Orta Anadolu kaynaklı tularemi olgularının değerlendirilmesi. Mikrobiyol Bul 2011;45:762-4.
34. Engin A, Altuntaş EE, Cankorkmaz L, Kaya A, Elaldı N, Şimşek H, et al. Sivas ilinde saptanan iİlk tularemi salgını: 29 olgunun değerlendirilmesi. Klimik Dergisi 2011;24:17-23.
35. Ulu Kılıç A, Kılıç S, Sencan I, Ciçek Şentürk G, Gürbüz Y, Tütüncü EE, et al. 2011. İç Anadolu Bölgesinde Francisella tularensis alt tür halorctica’ya Bağlı Su Kaynaklı Bir Tularemi Salgını Mikrobiyol Bul 2011;45:234-47.
36. Yazgı H, Uyanık MH, Ertek M, Kılıç S, Kireçci E, Özden K, et al. Erzurum merkez ve kırsalında yaşayan riskli gruplarda tularemi seroprevalansı. MikrobiyolBül. 2011;45:67-74.
37. Uyar M, Cengiz B, Ünlü M, Çelebi B, Kılıç S, Eryılmaz A. Orta Anadolu Bölgesi illerinden hastanemize başvuran orofaringeal tularemi olgularının değerlendirilmesi. Mikrobiyol Bul 2011;45:58-66.
38. Tatman Otkun M, Akçalı A, Karadenizli A, Özbey N, Gazel D, Şener A, et al. Çanakkale’de hızla önlenen bir tularemi salgınının eEpidemiyolojik olarak değerlendirilmesi. Mikrobiyol Bul 2011;45:48-57.
39. Pata YS, Ünal M, Akbaş Y, Aydın Ö, Güner N. Tularemi; servikal lenfadenopatının alışılmadık bir nedeni: Tanı ve tedavi. Mersin Üniversitesi Tıp Fakültesi Derg 2004;5:452-5.
40. Atmaca S, Leblebicioğlu H, Ünal R, Tekat A, Şeşen T, Koyuncu M, et al. Samsun ve çevresinde görülen tularemi olguları. KBB-Forum 2005;4:171-2.
41. Gün BD, Bahadır B, Çelebi G, Numanoğlu G, Özdamar ŞO, Kuzey GM. Fine needle aspiration cytology findings in cases diagnosed as oropharyngeal tularemia lymphadenitis. Turkish Journal of Pathology 2007;23:38-42.
42. Erbay A, Baykam N, Güvener N, Diker S, Dokuzoğuz B, Yıldırmak T. Ankara yöresinde tularemi. İnfeksiyon Dergisi 2000;14:453-8.
43. Acicbe Ö, Aydın H, Levent Doğancı L. Havza/ Samsun Bölgesi’nde tularemi endemisi: İzlenen olguların retrospektif yorumu. İnfeksiyon Dergisi 2007;21:55-8.
44. Gürcan Ş, Tatman Otkun M, Otkun M, Arıkan O, Özer B, Gedikoğlu S. Bolu-Gerede-Yazıkara Köyü’nde tularemi epidemisi. İnfeksiyon Derg 2003;17:145-9.
45. Turhan V, Ardıç N, Sahinoğlu L, Besirbellioğlu BA, Gedikoğlu S. Ülkemizdeki tularemi olgularına genel bir bakış: Orofaringeal tipte seyreden bir salgın nedeniyle. Anatol J Clin Investig 2007;1:71-7.
46. Helvacı S, Akalın H, Oral HB, Gedikoğlu S. İki yüz beş tularemi olgusunun irdelenmesi. Bursa Devlet Hastanesi Bülteni 1999;15:1-6.
47. Tularaemia Annual Epidemiological Report for 2018. Available at: https://www.ecdc.europa.eu/en/ publications-data/tularaemia-annual-epidemiologicalreport-2018 [Accessed: December 12, 2020]
48. Willke A. Tularemi. ANKEM Derg 2006;20:222-6.
49. Tularemi İstatistik Verileri. Erişim adresi: https:// hsgm.saglik.gov.tr/tr/zoonotikvektorel-tularemi/ istatistik [Erişim tarihi: 12.12. 2020]
50. Splettstoesser WD, Piechotowski I, Buckendahl A, Frangoulidis D, Kaysser P, Kratzer W, et al. Tularemia in Germany: The tip of the iceberg? Epidemiol Infect 2009;137:736-43.
51. Jenzora A, Jansen A, Ranisch H, Lierz M, Wichmann O, Grunow R. Seroprevalence study of Francisella tularensis among hunters in Germany. FEMS Immunol Med Microbiol 2008;53:183-9.
52. Jacob D, Barduhn A, Tappe D, Rauch J, Heuner K, Hierhammer D, et al. Outbreak of tularemia in a group of hunters in germany in 2018-kinetics of antibody and cytokine responses. Microorganisms 2020;8:1645.
53. Karadenizli A, Forsman M, Şimşek H, Taner M, Öhrman C, Myrtennäs K, et al. Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012. Euro Surveill 2015;20:21136.
54. Simşek H, Taner M, Karadenizli A, Ertek M, Vahaboğlu H. Identification of Francisella tularensis by both culture and real-time TaqMan PCR methods from environmental water specimens in outbreak areas where tularemia cases were not previously reported. Eur J Clin Microbiol Infect Dis 2012;31:2353-7.