Araştırma Makalesi
The evaluation of second line drug susceptibilities and molecular epidemiological profiles of multidrug resistance Mycobacterium tuberculosis isolates isoleted from different region of Turkey
Öz
Introduction: This study was planned to determine the second line drug resistance and molecular epidemiological profiles of multidrug resistant Mycobacterium tuberculosis isolates isolated from different geographical regions of Turkey.
Material and Method: In our study, 63 MDR M. tuberculosis isolates were evaluated for the drug susceptibility sent from different tuberculosis laboratories of Turkey. Secondary antituberculosis drugs resistance was evaluated by indirect proportion method. Epidemiological origins were evaluated by using IS6110-RFLP and spoligotyping methods.
Results: Cycloserine, ethionamide, capreomycin, thiacetozone, ofloxacin, kanamsin and paraaminosalicylic acid resistance rates were 15.87%, 19.04%, 7.93%, 6.34%, 11.11%, 12.69% and 6.34.%, respectively. According to spoligotyping results, 11 different patterns were obtained, including 52 isolates consisting of 5 clusters and 11 patterns consisting of a single isolate. When we compared our results with the spoligotype database in the world; 42 of 52 isolates forming 5 clusters were identified as predefined spoligotypes (LAM7-TUR, LAM9, T clade). 10 isolates showed the characteristics of the U spoligotype family. Of the 11 isolates that produced 11 different patterns, 8 were Haarlem and T spoligotypes. It was found that 2 isolates had the characteristics of Orphan and 1 isolate had the characteristics of BOV family.
Conclusion: In our study, LAM7-TUR, LAM9, T clade spoligotype families are common in our country and in the world were determined.
Anahtar Kelimeler
M. tuberculosis multi-drug resistance IS6110 RFLP spoligotyping
Destekleyen Kurum
TUBITAK Health Sciences Research Group (SBAG)
Proje Numarası
SBAG-HD-63(105S321)
Kaynakça
- WH0. Global tuberculosis report 2019. Geneva: World HealthOrganization, 2020. https: //www.who.int/tb/publications/global_report/en/
- WHO Consolidated Guidelines on Tuberculosis Module 4: Treatment Drug-resistant Tuberculosis Treatment. Geneva, World Health Organization, 2020. https: //apps. who.int/iris/bitstream/handle/10665/332397/9789240007048-eng.pdf
- World HealthOrganization. Guidelines for the programmatic management of drug-resistant tuberculosis—2014.
- McBryde ES, Meehan MT, Doan TN, et al. The risk of global epidemic replacement with drug resistant M. tuberculosis strains. Int J Infect Dis 2017; 56: 14–20.
- Dheda K, Gumbo T, Maartens G, et al. The epidemiology, pathogenesis, transmission, diagnosis, andmanagement of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir Med 2017; 5: 291–360.
- Suchindran S, Brouwer ES, Van Rie A. Is HIV infection a risk factor for multi-drug resistant tuberculosis? A systematic review. PLoS One 2009; 4: e5561.
- Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med 2015; 3: 963–72.
- Uçar E, Kılıç A, Ceyhan I, et al. Ülkemizin yedi farklı bölgesinden 2003-2006 yılları arasında izole edilen Mycobacterium tuberculosis suşlarının majör antitüberküloz ilaçlara direnç oranları. Mikrobiyol Bült 2010; 44: 11-9.
- Türkiye’de Verem Savaş Raporu 2019. T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü, 2019.
- World Health Organization WHO treatment guidelines for drug-resistant tuberculosis 2016 update. WHO/HTM/TB 2016. 04. World Health Organization, Geneva, 2016.
- Handbook on TB laboratory diagnostic methods in the European Union. Technıcal Document.https: //www.ecdc.europa.eu/ sites/default/ files/ documents/ tuberculosis - laboratory-diagnostic-methods-eu.pdf.2016.
- Ulusal Tüberküloz Tanı Rehberi. T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu Başkanlığı Mikrobiyoloji Referans Laboratuvarları Daire Başkanlığı Ankara – 2014.
- Basil MV, Nair D. Molecular epidemiology of tuberculosis: Opportunities&challenges in disease control. Indian J Med Res 2017; 146: 11–14.
- Cannas A, Mazzarelli A, DiCaro A, Delogu G, Girardi E. Molecular typing of Mycobacterium tuberculosis strains: A fundamental tool for tuberculosis control and elimination. Infect Dis Rep 2016; 8: 6567.
- Jagielski T, Minias A, vanIngen J, et al. Methodological and clinical aspects of the molecular epidemiology of Mycobacterium tuberculosis and other mycobacteria. Clin Microbiol Rev 2016; 29: 239–90.
- Oudghiri A , Chaoui I, Elmzibri M. Molecular epidemiology of tuberculosis: a review of tools and applications. J InfectDis Ther 2018; 6: 386.
- Kato-Maeda M, Metcalfe JZ, Flores L. Genotyping of Mycobacterium tuberculosis: application İn epidemiologic studies. Future Microbiol 2011; 6: 203-16.
- Kubica GPW, Dye E, Cohn ML, Middlebrook G. Sputum digestion and decontamination with N-acetyl-L-cysteine-sodiumhydroxide for culture of mycobacteria. Am Rev Respir Dis 1993; 87: 775-80.
- Becton Dickinson. MGIT For BACTEC ™ MGIT 960 ™ TB System 2006.
- Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results.Eur Respir J 2005; 25: 564-9.
- Kocagöz T, Yılmaz E, Özkara Ş, et al. Detection of Mycobacterium tuberculosis in sputum samples by polymerase chain reaction using a simplified procedure. J Clin Microbiol 1993; 31: 1435-8.
- van Soolingen D, Hermans PW, de Haas PE, Soll DR, van Embden JD. Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol 1991; 29: 2578–86.
- Kamerbeek J, Schouls L, Kolk A, et al. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997; 35: 907–14.
- Aranaz A, Liebana E, Mateos A, Dominguez L, Cousins D. Restriction fragment length polymorphism and spacer oligonucleotide typing: a comparative analysis of fingerprinting strategies for Mycobacterium bovis. Vet Microbiol 1998; 61: 311–24.
- www.pasteur-guadeloupe.fr: 8081/sıtvıt_online
- Roring S, Brittain D, Bunschoten AE, et al. Spacer oligotyping of Mycobacterium bovis isolates compared to typing by restriction fragment length polymorphism using PGRS, DR and IS6110 probes. Vet Microbiol 1998; 61: 111–20.
- Sola C, Horgen L, Maisetti J, Devallois A, Goh KS, Rastogi N. Spoligotyping followed by double-repetitive-element PCR as rapid alternative to IS6110 fingerprinting for epidemiological studies of tuberculosis. J Clin Microbiol 1998; 36: 1122–4.
- Kayalı R, Çöplü N, Ceyhan İ, Ocak F, Çitil BE, Esen B. Çok ilaca dirençli Mycobacterium tuberculosis suşlarının minör antitüberküloz ilaçlara duyarlılığının saptanması. Mikrobiyol Bült 2006, 40: 1-7.
- Şimşek H, Tarhan, G , Cesur S. Evaluation of second-line antituberculosis drug susceptibilities of multidrug-resistant Mycobacterium tuberculosis complex isolates by E-test method. Mikrobiyol Bult 2015; 49: 47-55.
- Bektöre B, Haznedaroğlu T, Baylan O, et al. Investigation of Extensive Drug Resistance in Multidrug Resistance Tuberculosis Isolates. Mikrobiyol Bul 2013; 47: 59-70.
- Çiçek SC, Çavuşoğlu C, Burhanoğlu D, Özkalay N, Badak ZF, Bilgiç A. Susceptibility of Mycobacterium tuberculosis strains to first-line and second-line antituberculosis drugs in Ege University hospital. Turk J Med Sci 2001; 31: 395-400.
- Tumer F, Savran Ş. Memleketimizde 1992-93 yıllarında tüberküloz ilaçlarına direnç durumu 20. Turk tüberküloz ve göğüs hastalıkları kongresi 7-9 Nisan 1994 Antalya, 380-386.
- Osmanlıoğlu G. Türkiye’de tüberküloz ilaçlarında direnç durumu 19. Tüberküloz ve göğüs hastalıkları kongresi. Sivas, 1991; l58.
- Ozkutuk N, Surucuoglu S, Gazi H, Coskun M, Ozkutuk A, Ozbakkaloglu B. Second-line drug susceptibilities of multidrug-resistant Mycobacterium tuberculosis isolates in Aegeanregion-Turkey. Turk J Med Sci 2008; 38: 245-50.
- Pfyffer EG, Bonato AD, Ebrahimzadeh A et al. Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial Drugs by using the radyometric BACTEC 460 Technique and the proportion Method with Solid media. Clin Microbiol 1999; 37: 3179-86.
- WH0. Guidelines for surveillance of drug resistance in tuberculosis. 5th Edition, Geneva: World Health Organization, 2015.
- Cannas A, Mazzarelli A, DiCaro A, Delogu G, Girardi E. Molecular typing of Mycobacterium tuberculosis strains: a fundamental tool for tuberculosis control and elimination. Infect Dis Rep 2016; 8: 6567.
- Basil MV, Nair D. Molecular epidemiology of tuberculosis: Opportunities & challenges in disease control. Indian J Med Res 2017; 146: 11–4.
- Karagöz A, Hidayet Tütün H, Altintaş L, Alanbayi U, Yıldırım D, Kocak N. Molecular typing of drug-resistant Mycobacterium tuberculosis strains from Turkey. J Glob Antimicrob Resist 2020; 23: 130-4.
- Pourostadi M, Rashedi J, Poor BM, et al. Role of Molecular Epidemiology on Tuberculosis Control in the Middle East Countries: a Systematic Review and Meta-Analysis.Tanaffos 2018; 17: 223–32.
- Kısa O, Tarhan,G, Gunal S, et al. The distribution of spoligotyping defined genotypic lineages among drug-resistant M. tuberculosis complex clinical isolates in Ankara, Turkey, Plos One 2012; 7: e30331.
- Durmaz R, Ozerol IH, Durmaz B, Gunal S, Senoglu A, Evliyaoglu E. Primary drugresistance and molecular epidemiology of Mycobacterium tuberculosis isolates from patients in a population with high tuberculosis incidence in Turkey. Microb Drug Resist 2003; 9: 361-6.
- Gencer B, Shinnick MT. Molecular genotyping of Mycobacterium tuberculosis Isolates from Turkey. Am J Infec Dis.2005; 1: 5–11.
- Durmaz R, Zozio T, Gunal S, Allix C, Fauville-Dufaux M, Rastogi N. Population-based molecular epidemiological study of tuberculosis in Malatya. Turk J Clin Microbiol 2007; 45: 4027-35.
- Durmaz R, Zozio T, Gunal S, et al. Genetic diversity and major spoligotype families of drug-resistant Mycobacterium tuberculosis clinical isolates from different regions of Turkey. Infect Genet Evol 2007; 7: 513–9.
- Otlu B, Durmaz R, Gunal S, et al. Beijing/W and major spoligotype families of Mycobacterium tuberculosis strains isolated from tuberculosis patients in Eastern Turkey. New Microbiol 2009; 32: 255–63.
- Sinkov V, Ogarkov O, Mokrousov I, Bukin Y, Zhdanova S, Heysell SK. New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe. BMC Genomics 2018; 19: 762.
- Cavuşoğlu C, Yılmaz FF, Onmus IRD, Bozdemir T, Taslı H, Limoncu MH. Genotype distribution of Mycobacterium tuberculosis in the Aegean Region and associated demographic factors. Turk J Med Sci 2017; 47: 1593-601.
Yıl 2022,
Cilt: 4 Sayı: 1, 81 - 88, 24.01.2022
Öz
Proje Numarası
SBAG-HD-63(105S321)
Kaynakça
- WH0. Global tuberculosis report 2019. Geneva: World HealthOrganization, 2020. https: //www.who.int/tb/publications/global_report/en/
- WHO Consolidated Guidelines on Tuberculosis Module 4: Treatment Drug-resistant Tuberculosis Treatment. Geneva, World Health Organization, 2020. https: //apps. who.int/iris/bitstream/handle/10665/332397/9789240007048-eng.pdf
- World HealthOrganization. Guidelines for the programmatic management of drug-resistant tuberculosis—2014.
- McBryde ES, Meehan MT, Doan TN, et al. The risk of global epidemic replacement with drug resistant M. tuberculosis strains. Int J Infect Dis 2017; 56: 14–20.
- Dheda K, Gumbo T, Maartens G, et al. The epidemiology, pathogenesis, transmission, diagnosis, andmanagement of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. Lancet Respir Med 2017; 5: 291–360.
- Suchindran S, Brouwer ES, Van Rie A. Is HIV infection a risk factor for multi-drug resistant tuberculosis? A systematic review. PLoS One 2009; 4: e5561.
- Kendall EA, Fofana MO, Dowdy DW. Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir Med 2015; 3: 963–72.
- Uçar E, Kılıç A, Ceyhan I, et al. Ülkemizin yedi farklı bölgesinden 2003-2006 yılları arasında izole edilen Mycobacterium tuberculosis suşlarının majör antitüberküloz ilaçlara direnç oranları. Mikrobiyol Bült 2010; 44: 11-9.
- Türkiye’de Verem Savaş Raporu 2019. T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü, 2019.
- World Health Organization WHO treatment guidelines for drug-resistant tuberculosis 2016 update. WHO/HTM/TB 2016. 04. World Health Organization, Geneva, 2016.
- Handbook on TB laboratory diagnostic methods in the European Union. Technıcal Document.https: //www.ecdc.europa.eu/ sites/default/ files/ documents/ tuberculosis - laboratory-diagnostic-methods-eu.pdf.2016.
- Ulusal Tüberküloz Tanı Rehberi. T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu Başkanlığı Mikrobiyoloji Referans Laboratuvarları Daire Başkanlığı Ankara – 2014.
- Basil MV, Nair D. Molecular epidemiology of tuberculosis: Opportunities&challenges in disease control. Indian J Med Res 2017; 146: 11–14.
- Cannas A, Mazzarelli A, DiCaro A, Delogu G, Girardi E. Molecular typing of Mycobacterium tuberculosis strains: A fundamental tool for tuberculosis control and elimination. Infect Dis Rep 2016; 8: 6567.
- Jagielski T, Minias A, vanIngen J, et al. Methodological and clinical aspects of the molecular epidemiology of Mycobacterium tuberculosis and other mycobacteria. Clin Microbiol Rev 2016; 29: 239–90.
- Oudghiri A , Chaoui I, Elmzibri M. Molecular epidemiology of tuberculosis: a review of tools and applications. J InfectDis Ther 2018; 6: 386.
- Kato-Maeda M, Metcalfe JZ, Flores L. Genotyping of Mycobacterium tuberculosis: application İn epidemiologic studies. Future Microbiol 2011; 6: 203-16.
- Kubica GPW, Dye E, Cohn ML, Middlebrook G. Sputum digestion and decontamination with N-acetyl-L-cysteine-sodiumhydroxide for culture of mycobacteria. Am Rev Respir Dis 1993; 87: 775-80.
- Becton Dickinson. MGIT For BACTEC ™ MGIT 960 ™ TB System 2006.
- Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results.Eur Respir J 2005; 25: 564-9.
- Kocagöz T, Yılmaz E, Özkara Ş, et al. Detection of Mycobacterium tuberculosis in sputum samples by polymerase chain reaction using a simplified procedure. J Clin Microbiol 1993; 31: 1435-8.
- van Soolingen D, Hermans PW, de Haas PE, Soll DR, van Embden JD. Occurrence and stability of insertion sequences in Mycobacterium tuberculosis complex strains: evaluation of an insertion sequence-dependent DNA polymorphism as a tool in the epidemiology of tuberculosis. J Clin Microbiol 1991; 29: 2578–86.
- Kamerbeek J, Schouls L, Kolk A, et al. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997; 35: 907–14.
- Aranaz A, Liebana E, Mateos A, Dominguez L, Cousins D. Restriction fragment length polymorphism and spacer oligonucleotide typing: a comparative analysis of fingerprinting strategies for Mycobacterium bovis. Vet Microbiol 1998; 61: 311–24.
- www.pasteur-guadeloupe.fr: 8081/sıtvıt_online
- Roring S, Brittain D, Bunschoten AE, et al. Spacer oligotyping of Mycobacterium bovis isolates compared to typing by restriction fragment length polymorphism using PGRS, DR and IS6110 probes. Vet Microbiol 1998; 61: 111–20.
- Sola C, Horgen L, Maisetti J, Devallois A, Goh KS, Rastogi N. Spoligotyping followed by double-repetitive-element PCR as rapid alternative to IS6110 fingerprinting for epidemiological studies of tuberculosis. J Clin Microbiol 1998; 36: 1122–4.
- Kayalı R, Çöplü N, Ceyhan İ, Ocak F, Çitil BE, Esen B. Çok ilaca dirençli Mycobacterium tuberculosis suşlarının minör antitüberküloz ilaçlara duyarlılığının saptanması. Mikrobiyol Bült 2006, 40: 1-7.
- Şimşek H, Tarhan, G , Cesur S. Evaluation of second-line antituberculosis drug susceptibilities of multidrug-resistant Mycobacterium tuberculosis complex isolates by E-test method. Mikrobiyol Bult 2015; 49: 47-55.
- Bektöre B, Haznedaroğlu T, Baylan O, et al. Investigation of Extensive Drug Resistance in Multidrug Resistance Tuberculosis Isolates. Mikrobiyol Bul 2013; 47: 59-70.
- Çiçek SC, Çavuşoğlu C, Burhanoğlu D, Özkalay N, Badak ZF, Bilgiç A. Susceptibility of Mycobacterium tuberculosis strains to first-line and second-line antituberculosis drugs in Ege University hospital. Turk J Med Sci 2001; 31: 395-400.
- Tumer F, Savran Ş. Memleketimizde 1992-93 yıllarında tüberküloz ilaçlarına direnç durumu 20. Turk tüberküloz ve göğüs hastalıkları kongresi 7-9 Nisan 1994 Antalya, 380-386.
- Osmanlıoğlu G. Türkiye’de tüberküloz ilaçlarında direnç durumu 19. Tüberküloz ve göğüs hastalıkları kongresi. Sivas, 1991; l58.
- Ozkutuk N, Surucuoglu S, Gazi H, Coskun M, Ozkutuk A, Ozbakkaloglu B. Second-line drug susceptibilities of multidrug-resistant Mycobacterium tuberculosis isolates in Aegeanregion-Turkey. Turk J Med Sci 2008; 38: 245-50.
- Pfyffer EG, Bonato AD, Ebrahimzadeh A et al. Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial Drugs by using the radyometric BACTEC 460 Technique and the proportion Method with Solid media. Clin Microbiol 1999; 37: 3179-86.
- WH0. Guidelines for surveillance of drug resistance in tuberculosis. 5th Edition, Geneva: World Health Organization, 2015.
- Cannas A, Mazzarelli A, DiCaro A, Delogu G, Girardi E. Molecular typing of Mycobacterium tuberculosis strains: a fundamental tool for tuberculosis control and elimination. Infect Dis Rep 2016; 8: 6567.
- Basil MV, Nair D. Molecular epidemiology of tuberculosis: Opportunities & challenges in disease control. Indian J Med Res 2017; 146: 11–4.
- Karagöz A, Hidayet Tütün H, Altintaş L, Alanbayi U, Yıldırım D, Kocak N. Molecular typing of drug-resistant Mycobacterium tuberculosis strains from Turkey. J Glob Antimicrob Resist 2020; 23: 130-4.
- Pourostadi M, Rashedi J, Poor BM, et al. Role of Molecular Epidemiology on Tuberculosis Control in the Middle East Countries: a Systematic Review and Meta-Analysis.Tanaffos 2018; 17: 223–32.
- Kısa O, Tarhan,G, Gunal S, et al. The distribution of spoligotyping defined genotypic lineages among drug-resistant M. tuberculosis complex clinical isolates in Ankara, Turkey, Plos One 2012; 7: e30331.
- Durmaz R, Ozerol IH, Durmaz B, Gunal S, Senoglu A, Evliyaoglu E. Primary drugresistance and molecular epidemiology of Mycobacterium tuberculosis isolates from patients in a population with high tuberculosis incidence in Turkey. Microb Drug Resist 2003; 9: 361-6.
- Gencer B, Shinnick MT. Molecular genotyping of Mycobacterium tuberculosis Isolates from Turkey. Am J Infec Dis.2005; 1: 5–11.
- Durmaz R, Zozio T, Gunal S, Allix C, Fauville-Dufaux M, Rastogi N. Population-based molecular epidemiological study of tuberculosis in Malatya. Turk J Clin Microbiol 2007; 45: 4027-35.
- Durmaz R, Zozio T, Gunal S, et al. Genetic diversity and major spoligotype families of drug-resistant Mycobacterium tuberculosis clinical isolates from different regions of Turkey. Infect Genet Evol 2007; 7: 513–9.
- Otlu B, Durmaz R, Gunal S, et al. Beijing/W and major spoligotype families of Mycobacterium tuberculosis strains isolated from tuberculosis patients in Eastern Turkey. New Microbiol 2009; 32: 255–63.
- Sinkov V, Ogarkov O, Mokrousov I, Bukin Y, Zhdanova S, Heysell SK. New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe. BMC Genomics 2018; 19: 762.
- Cavuşoğlu C, Yılmaz FF, Onmus IRD, Bozdemir T, Taslı H, Limoncu MH. Genotype distribution of Mycobacterium tuberculosis in the Aegean Region and associated demographic factors. Turk J Med Sci 2017; 47: 1593-601.
Toplam 48 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Research Articles |
| Yazarlar | |
| Proje Numarası | SBAG-HD-63(105S321) |
| Erken Görünüm Tarihi | 21 Ocak 2022 |
| Yayımlanma Tarihi | 24 Ocak 2022 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 4 Sayı: 1 |
Kaynak Göster
Üniversitelerarası Kurul (ÜAK) Eşdeğerliği: Ulakbim TR Dizin'de olan dergilerde yayımlanan makale [10 PUAN] ve 1a, b, c hariç uluslararası indekslerde (1d) olan dergilerde yayımlanan makale [5 PUAN]
- Dahil olduğumuz İndeksler (Dizinler) ve Platformlar sayfanın en altındadır.
Not: Dergimiz WOS indeksli değildir ve bu nedenle Q olarak sınıflandırılmamaktadır.
Yüksek Öğretim Kurumu (YÖK) kriterlerine göre yağmacı/şüpheli dergiler hakkındaki kararları ile yazar aydınlatma metni ve dergi ücretlendirme politikasını tarayıcınızdan indirebilirsiniz. https://dergipark.org.tr/tr/journal/3449/page/10809/update
Dergi Dizin ve Platformları
TR Dizin ULAKBİM, Google Scholar, Crossref, Worldcat (OCLC), DRJI, EuroPub, OpenAIRE, Turkiye Citation Index, Turk Medline, ROAD, ICI World of Journal's, Index Copernicus, ASOS Index, General Impact Factor, Scilit.