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Türkiye’de 2007 – 2008 İnfluenza Sezonunda Oseltamivir Dirençli İnfluenza A H1N1 Virüslerinin H274Y Mutasyonu ile Saptanması

Year 2012, Volume: 69 Issue: 1, 1 - 16, 01.03.2012

Abstract

Amaç: Kuzey yarım kürede 2007–2008 influenza sezonunun başlangıcından itibaren dahaönce tanımlanmış olan influenza A H1N1 virüsünün oseltamivir direncinin arttığısaptanmıştır. Bu direncin göstergesi, nöraminidaz NA geninin 274. aminoasidinin H274Y histidinden tirozine dönüşümü ile ortaya konmaktadır. Avrupa’da influenza A H1N1 suşları arasında oseltamivire direnç oranı %25 olarak saptanmıştır. Bu oran ülkeler arasında farklılık göstermekle birlikte Norveç’te en yüksek %67 , İspanya’da en düşük %2 olarak tespit edilmiştir. Bu çalışmada 2007-2008 influenza sezonunda Türkiye’deki influenza A H1N1 izolatlarında oseltamivir direncini tespit etmek amaçlanmıştır. Yöntem: Refik Saydam Hıfzıssıhha Merkezi Başkanlığı RSHMB Ulusal İnfluenza Merkezi’nde 2007 Kasım - 2008 Mayıs ayları arasında real-time RT-PCR ile test edilerek influenza A H1N1 pozitif olarak bulunan toplam 73 örnek arasından rastlantısal olarak 20 örnek seçilmiştir. Oseltamivir direncini tespit etmek için influenza A H1N1 suşlarının NA gen bölgesi 274. aminoasitini hedefleyen RT-PCR işlemi, histidinden tirozine dönüşümü göstermek için uygulanmıştır. İnfluenza virüslerinin NA geni sekanslanmış ve daha önceden tanımlanmış gen dizileri ile karşılaştırılarak direnç belirlenmiştir. Bulgular: Çalışmamızda değerlendirilen toplam 20 influenza A H1N1 izolatının iki %10 ’sinde oseltamivir direncinin göstergesi olan 274. N1 numaralandırmasında 275 aminoasitte histidinden H tirozine Y değişim saptanmıştır. NA segmentinin kısmi dizi analizi sonuçları National Center for Biotechnology Information NCBI GenBankasında GQ369800, GQ369799, GQ369798 giriş numaraları ile sunulmuştur. Sonuç: NA dizi analizi ile ülkemiz orta ve doğu kısımlarından gelen influenza A H1N1 suşlarının H274Y oseltamivir direncinin değerlendirilmesiyle Türkiye’de 2008 yılında nöraminidaz inhibitörlerine direncin görülmeye başlandığını belirlenmiştir.

References

  • 1. Avellon A, Cabrerizo M, Miguel T, Perez-Brena P, Tenorio A, Perez JL, et al. Widespread oseltamivir resistance in influenza A viruses (H1N1), South Africa Emerg Infect Dis, 2008; 14:1809-10.
  • 2. Ciancio BC, Meerhoff TJ, Kramarz P, Bonmarin I, Borgen K, Boucher CA, et al. Oseltamivir-resistant inluenza A (H1N1) viruses detected in Europe during season 2007-8 had epidemiologic and clinical characteristics similar to co-circulating susceptible A(H1N1) viruses. Euro Surveill, 2009; 14(46): pii 19412.
  • 3. Hauge SH, Dudman S, Borgen K, Lackenby A, Hungnes O. Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007-08. Emerg Infect Dis, 2009; 15: 155-62.
  • 4. Meijer A, Lackenby A, Hungnes O, Lina B, van der Werf S, Schweiger B, et al. Oseltamivir-resistant influenza viruses A (H1N1), Europe, 2007-08 season. Emerg Infect Dis, 2009; 15: 552-60.
  • 5. Mossong J, Opp M, Gerloff N, Hau P, Kremer J, Lackenby A. Emergence of oseltamivir-resistant influenza A H1N1 virus during the 2007-2008 winter season in Luxembourg: Clinical characteristics and epidemiology. Antiviral Res, 2009; 84: 91-4.
  • 6. Dharan NJ, Gubareva LV, Meyer JJ, OkomoAdhiambo M, McClinton RC, Marshall SA, et al. Infections with oseltamivir-resistant influenza A (H1N1) virus in the United States. JAMA, 2009; 301: 1034-41.
  • 7. Gerloff NA, Kremer JR, Mossong J, Opp M, Muller CP. Genomic Diversity of Oseltamivir-Resistant Influenza virus A (H1N1), Luxembourg, 2007-2008. Emerg Infect Dis, 2009; 15: 1523-4.
  • 8. Burrel S, Roncin L, Lafon ME, Fleury H. Oseltamivir susceptibility in South-Western France during the 2007-8 and 2008-9 influenza epidemics and the ongoing influenza pandemic 2009. Euro Surveill, 2009; 14(38): pii 19334.
  • 9. CDC.http://www.who.int/csr/resources/ publications/ swineflu/ realtimeptpcr/ en/index. html
  • 10. Wright KE, Wilson GAR, Novosad D, Dimock C, Tan D, Weber JM. Typing and subtyping of influenza viruses in clinical samples by PCR. J Clin Microbiol, 1995; 33: 1180–84.
  • 11. Vicente D, Cila G, Montes M, Mendiola J, PerezTrallero E. Rapid spread of drug-resistant inluenza A viruses in the Basque Country, Northern Spain, 2000-1 to 2008-9. Euro Surveill, 2009; 14(20): pii 19215.
  • 12. Carhan A, Altas AB, Albayrak N, Uyar Y. Influenza surveillance results in 2007-2008 winter season in nine provinces of Turkey. Mikrobiol Bul, 2009; 43(2): 235-41.
  • 13. Ciblak MA, Hasoksuz M, Escuret V, Valette M, Gul F, Bozkaya E, Badur S. Surveillance and oseltamivir resistance of human influenza A virus in Turkey during the 2007-2008 season. J Med Virol, 2009; 81(9): 1645-51.

Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey

Year 2012, Volume: 69 Issue: 1, 1 - 16, 01.03.2012

Abstract

Objective: In the beginning of the 2007-2008 influenza season in Northern Hemisphere, the frequency of influenza A H1N1 viruses bearing a previously defined oseltamivir resistance increased dramatically. This is conferring to the amino acid exchange from histidine to tyrosine at position 274 H274Y in neuraminidase NA gene. The overall frequency of oseltamivir resistance in influenza A H1N1 strains in Europe was reported as being 25%. Although it varied between countries, it was shown that the highest percentage was in Norway 67% , and the lowest was in Spain 2% . In this study, it was aimed to evaluate the oseltamivir resistance in influenza A H1N1 isolates from Turkey during the 20072008 influenza season.Method: During November 2007 – May 2008, 20 samples were randomly selected between 73 influenza A H1N1 positive samples detected with real-time RT- PCR in National Influenza Center NIC of Refik Saydam National Public Health Agency RSNPHA . To detect such resistant viruses in Turkey, an RT-PCR assay was performed targeting amino acid position at 274 in NA gene of H1N1 influenza strain to investigate the presence or absence of histidine to tyrosine mutation The NA genes of influenza, viruses were sequenced. The presence of resistance was inferred by comparison with published sequences and known resistant mutations. Results:In our study, the histidine H to tyrosine Y substitution at position 274 275 in N1 numbering of the NA gene was evaluated. The change indicating resistance to oseltamivir was observed in two isolates of the total 20 influenza A H1N1 strains 10% . The partial sequence analysis results of NA segments were submitted to the National Center for Biotechnology Information NCBI GenBank with accession numbers GQ369800, GQ369799, GQ369798. Conclusion: Resistance to neuraminidase inhibitors was determined by NA gene sequencing in the isolates of A/H1N1 strains taken from central and eastern parts of Turkey by monitoring the presence of H274Y oseltamivir-resistant in 2008.

References

  • 1. Avellon A, Cabrerizo M, Miguel T, Perez-Brena P, Tenorio A, Perez JL, et al. Widespread oseltamivir resistance in influenza A viruses (H1N1), South Africa Emerg Infect Dis, 2008; 14:1809-10.
  • 2. Ciancio BC, Meerhoff TJ, Kramarz P, Bonmarin I, Borgen K, Boucher CA, et al. Oseltamivir-resistant inluenza A (H1N1) viruses detected in Europe during season 2007-8 had epidemiologic and clinical characteristics similar to co-circulating susceptible A(H1N1) viruses. Euro Surveill, 2009; 14(46): pii 19412.
  • 3. Hauge SH, Dudman S, Borgen K, Lackenby A, Hungnes O. Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007-08. Emerg Infect Dis, 2009; 15: 155-62.
  • 4. Meijer A, Lackenby A, Hungnes O, Lina B, van der Werf S, Schweiger B, et al. Oseltamivir-resistant influenza viruses A (H1N1), Europe, 2007-08 season. Emerg Infect Dis, 2009; 15: 552-60.
  • 5. Mossong J, Opp M, Gerloff N, Hau P, Kremer J, Lackenby A. Emergence of oseltamivir-resistant influenza A H1N1 virus during the 2007-2008 winter season in Luxembourg: Clinical characteristics and epidemiology. Antiviral Res, 2009; 84: 91-4.
  • 6. Dharan NJ, Gubareva LV, Meyer JJ, OkomoAdhiambo M, McClinton RC, Marshall SA, et al. Infections with oseltamivir-resistant influenza A (H1N1) virus in the United States. JAMA, 2009; 301: 1034-41.
  • 7. Gerloff NA, Kremer JR, Mossong J, Opp M, Muller CP. Genomic Diversity of Oseltamivir-Resistant Influenza virus A (H1N1), Luxembourg, 2007-2008. Emerg Infect Dis, 2009; 15: 1523-4.
  • 8. Burrel S, Roncin L, Lafon ME, Fleury H. Oseltamivir susceptibility in South-Western France during the 2007-8 and 2008-9 influenza epidemics and the ongoing influenza pandemic 2009. Euro Surveill, 2009; 14(38): pii 19334.
  • 9. CDC.http://www.who.int/csr/resources/ publications/ swineflu/ realtimeptpcr/ en/index. html
  • 10. Wright KE, Wilson GAR, Novosad D, Dimock C, Tan D, Weber JM. Typing and subtyping of influenza viruses in clinical samples by PCR. J Clin Microbiol, 1995; 33: 1180–84.
  • 11. Vicente D, Cila G, Montes M, Mendiola J, PerezTrallero E. Rapid spread of drug-resistant inluenza A viruses in the Basque Country, Northern Spain, 2000-1 to 2008-9. Euro Surveill, 2009; 14(20): pii 19215.
  • 12. Carhan A, Altas AB, Albayrak N, Uyar Y. Influenza surveillance results in 2007-2008 winter season in nine provinces of Turkey. Mikrobiol Bul, 2009; 43(2): 235-41.
  • 13. Ciblak MA, Hasoksuz M, Escuret V, Valette M, Gul F, Bozkaya E, Badur S. Surveillance and oseltamivir resistance of human influenza A virus in Turkey during the 2007-2008 season. J Med Virol, 2009; 81(9): 1645-51.
There are 13 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Ahmet Çarhan This is me

Nurhan Albayrak This is me

Ayşe Başak Altaş This is me

Yavuz Uyar This is me

Etem Özkaya This is me

Publication Date March 1, 2012
Published in Issue Year 2012 Volume: 69 Issue: 1

Cite

APA Çarhan, A., Albayrak, N., Altaş, A. B., Uyar, Y., et al. (2012). Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey. Türk Hijyen Ve Deneysel Biyoloji Dergisi, 69(1), 1-16.
AMA Çarhan A, Albayrak N, Altaş AB, Uyar Y, Özkaya E. Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey. Turk Hij Den Biyol Derg. March 2012;69(1):1-16.
Chicago Çarhan, Ahmet, Nurhan Albayrak, Ayşe Başak Altaş, Yavuz Uyar, and Etem Özkaya. “Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses With H274Y Mutation During the 2007 - 2008 Influenza Season in Turkey”. Türk Hijyen Ve Deneysel Biyoloji Dergisi 69, no. 1 (March 2012): 1-16.
EndNote Çarhan A, Albayrak N, Altaş AB, Uyar Y, Özkaya E (March 1, 2012) Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey. Türk Hijyen ve Deneysel Biyoloji Dergisi 69 1 1–16.
IEEE A. Çarhan, N. Albayrak, A. B. Altaş, Y. Uyar, and E. Özkaya, “Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey”, Turk Hij Den Biyol Derg, vol. 69, no. 1, pp. 1–16, 2012.
ISNAD Çarhan, Ahmet et al. “Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses With H274Y Mutation During the 2007 - 2008 Influenza Season in Turkey”. Türk Hijyen ve Deneysel Biyoloji Dergisi 69/1 (March 2012), 1-16.
JAMA Çarhan A, Albayrak N, Altaş AB, Uyar Y, Özkaya E. Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey. Turk Hij Den Biyol Derg. 2012;69:1–16.
MLA Çarhan, Ahmet et al. “Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses With H274Y Mutation During the 2007 - 2008 Influenza Season in Turkey”. Türk Hijyen Ve Deneysel Biyoloji Dergisi, vol. 69, no. 1, 2012, pp. 1-16.
Vancouver Çarhan A, Albayrak N, Altaş AB, Uyar Y, Özkaya E. Detection of Oseltamivir-Resistant Influenza A H1N1 Viruses with H274Y Mutation during the 2007 - 2008 Influenza Season in Turkey. Turk Hij Den Biyol Derg. 2012;69(1):1-16.