:: Volume 30, Issue 3 (8-2022) ::
Journal of Ilam University of Medical Sciences 2022, 30(3): 55-61 Back to browse issues page
Determination of Oseltamivir Resistance Level by an H275Y Genotyping Assay among Influenza A (H1N1) Viruses in Hamadan Province, Iran
Shahab Mahmoudvand1 , Razieh Amini * 2, Farid Azizi Jalilian1 , Mojtaba Hedayat Yaghoobi3 , Masoumeh Javaheri4 , Iraj Sedighi5 , Mojgan Mamani6 , Razieh Ezati7 , Jalaledin Amiri4 , Massoud Saidijam8
1- Dept of Virology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2- Dept of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran , ra.amini@umsha.ac.ir
3- Dept of Infectious Diseases, School of Medicine, Alborz University of Medical Sciences, Alborz, Iran
4- Health Deputy, Hamadan University of Medical Sciences, Hamadan, Iran
5- Dept of Pediatric, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
6- Dept of Infectious Diseases, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
7- Dept of Molecular Virology, Farzan Pathobiology and Molecular Laboratory, Hamadan, Iran
8- Dept of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract:   (1182 Views)
Introduction: Epidemics and deaths caused by influenza viruses are an important concern worldwide. The use of neuraminidase inhibitors such as oseltamivir is an effective and valuable way to treat the diseases caused by these viruses. However, the mutation in several parts of the gene leads to the emergence of drug-resistant strains, and an ever-increasing rise in drug-resistant strains is a global problem. Histidine-to-tyrosine mutation at position 275 (H275Y) of neuraminidase protein is one of the most common oseltamivir resistance mutations. This study aimed to detect H275Y mutation in influenza A (H1N1) virus circulating in the Hamadan province of Iran using real-time polymerase chain reaction  (RT-PCR).
Material & Methods: This cross-sectional study was conducted on 110 swab samples isolated from patients with suspected influenza virus infection between 2015 and 2016. Ribonucleic acid (RNA) was extracted from samples and the RT-PCR method was used to determine virus types and subtypes. The positive samples were evaluated for detection of H275Y mutation using RT-PCR.
(Ethic code: IR.UMSHA.REC.1400.917)
Findings: Out of 110 patients in this study, 50 (45%) were females and 60 (55%) were males. The mean±SD age of participants was 40.74±2.42 years. Influenza A (H1N1) virus was found in 22 (20%) out of 110 patients, including 9/50 (18%) females and 13/60 (21.7%) males. There was no significant relationship between the virus and gender (P=0.81). No drug resistance related to H275Y mutation was observed in 22 positive cases.
Discussion & Conclusion: The findings indicated that no drug resistance mutations have occurred, and oseltamivir is still an appropriate option to treat infections caused by the influenza virus in Hamadan province, Iran. However, due to the increasing number of resistant strains, an annual review of oseltamivir resistance is recommended and further studies are needed in this regard.
Keywords: Drug resistance, Influenza A (H1N1) virus, Oseltamivir
Full-Text [PDF 1213 kb]   (518 Downloads)    
Type of Study: Research | Subject: virology
Received: 2019/10/8 | Accepted: 2019/11/3 | Published: 2022/08/6
1. Jackson RJ, Cooper KL, Tappenden P, Rees A, Simpson EL, Read RC, et al. Oseltamivir, zanamivir and amantadine in the prevention of influenza: a systematic review. J Infect 2011; 62:14-25. doi: 10.1016/j.jinf.2010.10.003.
2. Cox N, Subbarao K. Global epidemiology of influenza: past and present. Annu Rev Med. 2000;51:407-21. doi: 10.1146/annurev.med.51.1. 407.
3. Fischer WA, 2nd, Gong M, Bhagwanjee S, Sevransky J. Global burden of influenza as a cause of cardiopulmonary morbidity and mortality. Glob heart 2014; 9:325-36. doi: 10.1016/j.gheart.2014.08.004.
4. Bouvier NM, Palese P. The biology of influenza viruses. Vaccine. 2008;26: D49-D53. doi: 10.1016/j.vaccine.2008.07.039.
5. Das K, Aramini JM, Ma L-C, Krug RM, Arnold E. Structures of influenza A proteins and insights into antiviral drug targets. Nat Struct Mol Biol 2010; 17:530-8. doi: 10.1038/nsmb.1779.
6. Ikematsu H, Kawai N. Laninamivir octanoate: a new long-acting neuraminidase inhibitor for the treatment of influenza. Expert Rev Anti Infect Ther 2011; 9:851-7. doi: 10.1586/eri.11.112.
7. Kohno S, Kida H, Mizuguchi M, Hirotsu N, Ishida T, Kadota J, et al. Intravenous peramivir for treatment of influenza A and B virus infection in high-risk patients. Antimicrob Agents Chemother 2011;55:2803-12. doi: 10.1128/AAC. 01718-10.
8. Dapat IC, Dapat C, Baranovich T, Suzuki Y, Kondo H, Shobugawa Y, et al. Genetic characterization of human influenza viruses in the pandemic (2009–2010) and post-pandemic (2010–2011) periods in Japan. PLoS One. 2012;7: e36455. doi: 10.1371/journal.pone.0036455.
9. Chidlow GR, Harnett GB, Williams SH, Tempone SS, Speers DJ, Hurt AC, et al. The detection of oseltamivir-resistant pandemic influenza A/H1N1 2009 viruses using a real-time RT-PCR assay. J Virol Methods 2010; 169:47-51. doi: 10.1016/j.jviromet.2010.06.014.
10. Bai GR, Chittaganpitch M, Kanai Y, Li YG, Auwanit W, Ikuta K, et al. Amantadine-and oseltamivir-resistant variants of influenza A virus in Thailand. Biochem Biophys Res Commun 2009;390:897-901. doi: 10.1016/j.bbrc.2009. 10.071.
11. Moradi A, Nadji SA, Tabarsi P, Hashemian SM, Marjani M, Sigaroodi A, et al. Prevalence of Oseltamivir-Resistant 2009 H1N1 Influenza Virus among Patients with Pandemic 2009 H1N1 Influenza infection in NRITLD, Tehran, Iran. Tanaffos 2011; 10:8
12. Pontoriero A, Baumeister E, Campos AM, Savy VL. Virological surveillance and antiviral resistance of human influenza virus in Argentina, 2005-2008. Rev Panam Salud Publica 2011;30:634-40. doi: 10.1590/s1020-498920110 01200023.
13. Smith JR, Rayner CR, Donner B, Wollenhaupt M, Klumpp K, Dutkowski R. Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience. Adv Ther 2011; 28:927-59. doi: 10.1007/s12325-011-0072-7.
14. Gioula G, Melidou A, Exindari M, Papoutsi N, Chatzidimitriou D, Dotis J, et al. Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus in Northern Greece. Hippokratia 2011; 15:272.
15. Takayama I, Nakauchi M, Fujisaki S, Odagiri T, Tashiro M, Kageyama T. Rapid detection of the S247N neuraminidase mutation in influenza A (H1N1) pdm09 virus by one-step duplex RT-PCR assay. J Virol Methods 2013; 188:73-5. doi: 10.1016/j.jviromet.2012.12.005.
16. Okomo‐Adhiambo M, Sheu TG, Gubareva LV. Assays for monitoring susceptibility of influenza viruses to neuraminidase inhibitors. Influenza Other Respir Viruses 2013;7:44-9. doi: 10.1111/ irv.12051.
17. Choi W-Y, Kim S, Lee N, Kwon M, Yang I, Kim M-J, et al. Amantadine-resistant influenza A viruses isolated in South Korea from 2003 to 2009. Antiviral Res 2009; 84:199-202. doi: 10.1016/j.antiviral.2009.08.006.
18. Jandaghi N, Azad TM, Nadji S, Yavarian J, Naseri M, Salimi V, et al. Sequence and phylogenetic analyses of neuraminidase gene of Iranian seasonal influenza H1N1 viruses from 2005-2009 and corresponding vaccine strains. Acta Virol 2010; 54:205-10. doi: 10.4149/av_ 2010_03_205.
19. Jacks A, Ollgren J, Ziegler T, Lyytikäinen O. Influenza-associated hospitalisations in Finland from 1996 to 2010: unexpected age-specific burden during the influenza A (H1N1) pdm09 pandemic from 2009 to 2010. Eurosurveillance 2012; 17:20276.
20. Khodadad N, Moattari A, Shamsi Shahr Abadi M, Kadivar MR, Sarvari J, Tavakoli F, et al. Prevalence of Influenza A(H1N1) pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013. Jundishapur J Microbiol 2015;8: e23690-e. doi: 10.5812/jjm.23690.
21. Zambon MC. Surveillance for antiviral resistance. Influenza Other Respir Viruses 2013;7:37-43. doi.org/10.1111/irv.12050.
22. Zaraket H, Kondo H, Tabet C, Hanna-Wakim R, Suzuki Y, Dbaibo GS, et al. Genetic diversity and antiviral drug resistance of pandemic H1N1 2009 in Lebanon. J Clin Virol 2011; 51:170-4. doi: 10.1016/j.jcv.2011.04.001.
23. Yang JR, Huang YP, Chang FY, Hsu LC, Huang HY, Pan YT, et al. Characterization of oseltamivir‐resistant influenza A (H1N1) pdm09 viruses in Taiwan in 2009–2011. J Med Virol 2013; 85:379-87. doi: 10.1002/jmv.23482.
24. Nguyen HT, Trujillo AA, Sheu TG, Levine M, Mishin VP, Shaw M, et al. Analysis of influenza viruses from patients clinically suspected of infection with an oseltamivir resistant virus during the 2009 pandemic in the United States. Antiviral Res 2012; 93:381-6. doi: 10.1016/j.antiviral. 2012.01.006.
25. Whitley RJ, Boucher CA, Lina B, Nguyen-Van-Tam JS, Osterhaus A, Schutten M, et al. Global assessment of resistance to neuraminidase inhibitors, 2008–2011: The Influenza Resistance Information Study (IRIS). Clin Infect Dis 2013; 56:1197-205. doi: 10.1093/cid/cis1220.

XML   Persian Abstract   Print

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 30, Issue 3 (8-2022) Back to browse issues page