Tokat İlinde Fatal ve Fatal Olmayan Olgularda Kırım Kongo Kanamalı Ateşi Virüsünün Moleküler Analizi

Amaç: Kırım Kongo Kanamalı Ateşi (KKKA), ülkemizde 2002’den beri görülmekte ve %5 ölüm oranı ile seyretmektedir. Çalışmada, Türkiye’de ençok olgu bildirimi yapan il olan Tokat’ın ilçelerinden toplanan hasta serumlarında saptanan KKKA virüslerinin genomlarının M segmentlerindefataliteden sorumlu olabilecek herhangi bir farklılık olup olmadığının ortaya çıkarılması amaçlandı.Gereç ve Yöntem: KKKA olgularının en çok görüldüğü Mart-Ağustos 2014 döneminde Tokat’ın ilçelerinden başvuran dokuzu eks olan, 10’u şifa iletaburcu olan 19 hasta çalışmaya alındı. Viral RNA elde edilerek, M segment bölgesi PCR ile çoğaltılarak saflaştırıldı ve sekans analizine tabi tutuldu.Bulgular: Elde edilen M segment dizileri Avrupa grubuna girmekteydi, Rusya ve Kosova virüsleri ile yakın ilişki saptandı, hatta filogenetik ağaçtaaynı dal altında toplandı. Ancak 19 alttipten yedisi ayrı bir grup oluşturdu. Bu yedi alt tipte Kosova Hoti genotipinde olduğu gibi R1532K mutasyonu,yine Kosova ve Rusya genotiplerinde bulunan ancak Türkiye’den bildirilen diğer genotiplerde bulunmayan L1601F mutasyonu gözlendi ve bu nedenleayrı bir alt grup olarak tanımlandı.Sonuç: Bu çalışmada Almus’ta yaşayan ve karı koca olan; M segment analizi Turkey/Almus01/2014 olarak aynı çıkan hastalardan birinin eks olmasıdiğerinin şifa ile taburcu olması fataliteden sadece viral suşun değil bireysel faktörlerin de olduğu görüşünü desteklemektedir. Belli dönemlerdefatalite oranının arttığı şüphesi doğsa da her sezon bitiminde fatalite oranının aynı kalması virüste fataliteyi arttıracak bir mutasyonun henüzgelişmediğini düşündürmektedir, bu çalışmada elde edilen veriler bu görüşü desteklemektedir.

Molecular Analysis of Crimean-Congo Hemorrhagic Fever Virus Among Fatal and Non-fatal Cases in Tokat Province

Objectives: Crimean-Congo hemorrhagic fever (CCHF) is seen in our country with fatality rate of 5% since 2002. It was aimed to reveal if there were any differences responsible from fatalities in M segments of CCHF viruses detected in patients’ sera in Tokat province, reporting the most of the cases in Turkey. Materials and Methods: Nineteen patients, applying to hospital whom, nine were later ex and 10 were discharged with cure, from the same regions of Tokat districts between March to August 2014, which is the period of most number of CCHFV cases reported, were included. Viral RNA was isolated, M segment region was amplified and sequence analysis was performed. Results: Obtained M segment nucleotide sequences were found to be in Europe clade having close relation with Russian and Kosovo strains on the same branches of the phylogenetic tree. Seven out of 19 viruses were in a different group because they had R1532K mutation like Russian and Kosovo strains and L1601F mutation which was not found to exist in the genotypes reported from Turkey, before. Conclusion: In this study, Turkey/Almus01/2014 M segment analysis was found identical in a couple living in Almus, whom one of them had died while one was discharged from hospital with cure, suggesting individual factors were also responsible from fatality, not only viral strain. On certain periods although suspicion of high mortality rate occurs, at the end of each disease season, fatality stays on the same rate, suggesting there are not any viral mutations increasing fatality. Data on this study support this hypothesis.

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1. Bente DA, Forrester NL, Watts DM, et al. Crimean-Congo hemorrhagic fever: History, epideagar miology, pathogenesis, clinical syndrome and genetic diversity. Antivir Res. 2013;100:159-189.
2. Lukashev AN, Klimentov AS, Smirnova SE, et al. Phylogeography of Crimean Congo Hemorrhagic Fever Virus. PLoS One. 2016;11:e0166744.
3. Papa A, Tsergouli K, Tsioka K, et al. Crimean-Congo Hemorrhagic Fever: TickHost-Virus Interactions. Front Cell Infect Microbiol. 2017;7:213.
4. Ergonul O, Whıtehouse Ca. Crimean-Congo Hemorrhagic Fever: A Global Perspective. The Netherlands. Springer. 2007;219-212.
5. Salehi-Vaziri M, Baniasadi V, Jalali T, et al. The first fatal case of CrimeanCongo Hemorrhagic Fever due to AP92 like strain of Crimean-Congo Hemorrhagic Fever virus. Jpn J Infect Dis. 2016;69.
6. Ozkaya E, Dincer E, Carhan A, et al. Molecular epidemiology of Crimean– Congo hemorrhagic fever virus in Turkey: Occurrence of local topotype. Virus Res. 2010;149:64-70.
7. Hasanoglu I, Guner R, Carhan A, et al. Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load. J Clin Virol. 2016;75:42-46.
8. Hawman DW, Feldmann H. Recent advances in understanding CrimeanCongo hemorrhagic fever virus. F1000Res. 2018;7. pii: F1000 Faculty Rev 1715.
9. Kuhn JH, Seregin SV, Morzunov SP, et al. Genetic analysis of the M RNA segment of Crimean-Congo hemorrhagic fever virus strains involved in the recent outbreaks in Russia. Archives of Virology. 2004;149:pp2199-2213.
10. Xia X. DAMBE5: A comprehensive software package for data analysis in molecular biology and evolution. Mol Biol Evol. 2013;30:1720-1728.
11. Tamura K, Stecher G, Peterson D, et al. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30:2725-2729.
12. Bayrakdar F, Yagci Caglayik D. Crimean-Congo hemorrhagic fever virus isolate Turkey/Almus01/2014 glycoprotein precursor, gene, partial cds GenBank: KT266832.1 https://www.ncbi.nlm.nih.gov/nuccore/KT266832
13. Bayrakdar,F. and Yagci Caglayik,D Crimean-Congo hemorrhagic fever virus isolate Turkey/Tokat05/2014 glycoprotein precursor, gene, partial cds GenBank: KT266848.1 https://www.ncbi.nlm.nih.gov/nuccore/KT266848
14. Venter M, Madhi SA, Tiemessen CT, et al. Genetic diversity and molecular epidemiology of respiratory syncytial virus over four consecutive seasons in South Africa: identification of new subgroup A and B genotypes. J Gen Virol. 2001;82:2117-2124.
15. Ozdarendeli A, Aydin K, Tonbak S, et al. Genetic analysis of the M RNA segment of Crimean-Congo hemorrhagic fever virus strains in Turkey. Arch Virol. 2008;153:37-44.
16. Fajs L, Jakupi X, Ahmeti S, et al. Molecular Epidemiology of Crimean-Congo Hemorrhagic Fever Virus in Kosovo. PLoS Negl Trop Dis. 2014;8:e2647.
17. Estrada-Peña A, Vatansever Z, Gargili A, et al. The trend towards habitat fragmentation is the key factor driving the spread of Crimean-Congo haemorrhagic fever. Epidemiol Infect. 2010;138:1194-1203.
18. Gargili A, Estrada-Peña A, Spengler JR, et al. The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies. Antiviral Res. 2017;144:93-119.
19. Rodriguez LL, Maupin GO, Ksiazek TG, et al. Molecularinvestigationofamultisource outbreak of Crimean-Congo hemorrhagic fever in the UnitedArab Emirates. Am J Trop Med Hyg. 1997;57:512-518.