Objective: Among all hepatitis C virus (HCV) infections, subtype 3a is the most common genotype in Thailand. This study investigates the molecular epidemiology and epidemic history of HCV subtype 3a in Thailand. Methods: Three hundred and fifty-six serum samples were collected from HCV-infected Thai patients. The virus was isolated, after which the core and NS5B regions were sequenced. Subsequently, the HCV genotype was classified by phylogenetic analysis based on the core and NS5B regions. Molecular evolution analysis of HCV subtype 3a was estimated using BEAST (Bayesian Evolutionary Analysis by Sampling Trees) v.1.5.4. Results: Based on our phylogenetic analyses, subtype 3a (38.5%) was the most prevalent, followed by 1a (21%), 1b (13.8%), genotype 6 (19.9%) [comprised of subtypes 6e (0.3%), 6f (11%), 6i (1.9%), 6j (1.9%) and 6n (4.8%)] and 3b (5.6%). Our phylogenetic tree indicates the existence of a specific group of HCV subtype 3a strains in the Thai population. Molecular evolutionary analysis dated the most recent common ancestor of the Thai HCV subtype 3a strains as existing approximately 200 ago, and a Bayesian skyline plot showed that this particular strain spread to Thailand during the mid-1970s and early 1980s. This period overlaps with the Vietnam War (1955-1975) and the widespread use of injection stimulants introduced by the US Army during this time. Conclusion: The estimated history of HCV subtype 3a infection in Thailand may help to predict the future burden of HCV-related diseases and facilitate better public health control and surveillance.

1.
Lavanchy D: The global burden of hepatitis C. Liver Int 2009;29:74-81.
2.
Hoofnagle JH: Course and outcome of hepatitis C. Hepatology 2002;36:S21-S29.
3.
Seeff LB: Natural history of chronic hepatitis C. Hepatology 2002;36:S35-S46.
4.
Trinchet JC, Ganne-Carrie N, Nahon P, N'Kontchou G, Beaugrand M: Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver disease. World J Gastroenterol 2007;13:2455-2460.
5.
Fattovich G, Stroffolini T, Zagni I, Donato F: Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127:S35-S50.
6.
Yoshizawa H: Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology 2002;62:8-17.
7.
Simmonds P, Bukh J, Combet C, Deleage G, Enomoto N, Feinstone S, Halfon P, Inchauspe G, Kuiken C, Maertens G, Mizokami M, Murphy DG, Okamoto H, Pawlotsky JM, Penin F, Sablon E, Shin IT, Stuyver LJ, Thiel HJ, Viazov S, Weiner AJ, Widell A: Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005;42:962-973.
8.
Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B, Beall E, Yap PL, Kolberg J, Urdea MS: Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993;74:2391-2399.
9.
Pybus OG, Drummond AJ, Nakano T, Robertson BH, Rambaut A: The epidemiology and iatrogenic transmission of hepatitis C virus in Egypt: a bayesian coalescent approach. Mol Biol Evol 2003;20:381-387.
10.
Simmonds P: Genetic diversity and evolution of hepatitis C virus - 15 years on. J Gen Virol 2004;85:3173-3188.
11.
Khan A, Tanaka Y, Azam Z, Abbas Z, Kurbanov F, Saleem U, Hamid S, Jafri W, Mizokami M: Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan. J Med Virol 2009;81:1189-1197.
12.
Sunanchaikarn S, Theamboonlers A, Chongsrisawat V, Yoocharoen P, Tharmaphornpilas P, Warinsathien P, Sinlaparatsamee S, Paupunwatana S, Chaiear K, Khwanjaipanich S, Poovorawan Y: Seroepidemiology and genotypes of hepatitis C virus in Thailand. Asian Pac J Aller Immunol 2007;25:175-182.
13.
Zein NN: Clinical significance of hepatitis C virus genotypes. Clin Microbiol Rev 2000;13:223-235.
14.
Akkarathamrongsin S, Praianantathavorn K, Hacharoen N, Theamboonlers A, Tangkijvanich P, Tanaka Y, Mizokami M, Poovorawan Y: Geographic distribution of hepatitis C virus genotype 6 subtypes in Thailand. J Med Virol 2010;82:257-262.
15.
Elkady A, Tanaka Y, Kurbanov F, Sugauchi F, Sugiyama M, Khan A, Sayed D, Moustafa G, Abdel-Hameed AR, Mizokami M: Genetic variability of hepatitis C virus in South Egypt and its possible clinical implication. J Med Virol 2009;81:1015-1023.
16.
Lu L, Nakano T, Li C, Fu Y, Miller S, Kuiken C, Robertson BH, Hagedorn CH: Hepatitis C virus complete genome sequences identified from China representing subtypes 6k and 6n and a novel, as yet unassigned subtype within genotype 6. J Gen Virol 2006;87:629-634.
17.
Romano CM, de Carvalho-Mello IM, Jamal LF, de Melo FL, Iamarino A, Motoki M, Pinho JR, Holmes EC, de Andrade Zanotto PM: Social networks shape the transmission dynamics of hepatitis C virus. PLoS One 2010;5: e11170.
18.
Pybus OG, Cochrane A, Holmes EC, Simmonds P: The hepatitis C virus epidemic among injecting drug users. Infect Genet Evol 2005;5:131-139.
19.
Kurbanov F, Tanaka Y, Avazova D, Khan A, Sugauchi F, Kan N, Kurbanova-Khudayberganova D, Khikmatullaeva A, Musabaev E, Mizokami M: Detection of hepatitis C virus natural recombinant RF1_2k/1b strain among intravenous drug users in Uzbekistan. Hepatol Res 2008;38:457-464.
20.
Shustov AV, Kochneva GV, Sivolobova GF, Grazhdantseva AA, Gavrilova IV, Akinfeeva LA, Rakova IG, Aleshina MV, Bukin VN, Orlovsky VG, Bespalov VS, Robertson BH, Netesov SV: Molecular epidemiology of the hepatitis C virus in western Siberia. J Med Virol 2005;77:382-389.
21.
Verachai V, Phutiprawan T, Theamboonlers A, Chinchai T, Tanprasert S, Haagmans BL, Osterhaus AD, Poovorawan Y: Prevalence and genotypes of hepatitis C virus infection among drug addicts and blood donors in Thailand. Southeast Asian J Trop Med Public Health 2002;33:849-851.
22.
Rosenberg NA, Nordborg M: Genealogical trees, coalescent theory and the analysis of genetic polymorphisms. Nat Rev Genet 2002;3:380-390.
23.
Pybus OG, Charleston MA, Gupta S, Rambaut A, Holmes EC, Harvey PH: The epidemic behavior of the hepatitis C virus. Science 2001;292:2323-2325.
24.
Jutavijittum P, Jiviriyawat Y, Yousukh A, Pantip C, Maneekarn N, Toriyama K: Genotypic distribution of hepatitis C virus in voluntary blood donors of northern Thailand. Southeast Asian J Trop Med Public Health 2009;40:471-479.
25.
Lwin AA, Shinji T, Khin M, Win N, Obika M, Okada S, Koide N: Hepatitis C virus genotype distribution in Myanmar: predominance of genotype 6 and existence of new genotype 6 subtype. Hepatol Res 2007;37:337-345.
26.
Hubschen JM, Jutavijittum P, Thammavong T, Samountry B, Yousukh A, Toriyama K, Sausy A, Muller CP: High genetic diversity including potential new subtypes of hepatitis C virus genotype 6 in Lao People's Democratic Republic. Clin Microbiol Infect 2011;17:E30-E34.
27.
Tanaka Y, Hanada K, Mizokami M, Yeo AE, Shih JW, Gojobori T, Alter HJ: Inaugural article: a comparison of the molecular clock of hepatitis C virus in the United States and Japan predicts that hepatocellular carcinoma incidence in the United States will increase over the next two decades. Proc Natl Acad Sci USA 2002;99:15584-15589.
28.
Nakano T, Lu L, He Y, Fu Y, Robertson BH, Pybus OG: Population genetic history of hepatitis C virus 1b infection in China. J Gen Virol 2006;87:73-82.
29.
Markov PV, Pepin J, Frost E, Deslandes S, Labbe AC, Pybus OG: Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa. J Gen Virol 2009;90:2086-2096.
30.
Tanaka Y, Kurbanov F, Mano S, Orito E, Vargas V, Esteban JI, Yuen MF, Lai CL, Kramvis A, Kew MC, Smuts HE, Netesov SV, Alter HJ, Mizokami M: Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology 2006;130:703-714.
31.
Theamboonlers A, Chinchai T, Bedi K, Jantarasamee P, Sripontong M, Poovorawan Y: Molecular characterization of hepatitis C virus (HCV) core region in HCV-infected Thai blood donors. Acta Virol 2002;46:169-173.
32.
Akkarathamrongsin S, Praianantathavorn K, Hacharoen N, Theamboonlers A, Tangkijvanich P, Poovorawan Y: Seroprevalence and genotype of hepatitis C virus among immigrant workers from Cambodia and Myanmar in Thailand. Intervirology 2011;54:10-16.
33.
Kuiken C, Yusim K, Boykin L, Richardson R: The Los Alamos hepatitis C sequence database. Bioinformatics 2005;21:379-384.
34.
Mizokami M, Tanaka Y, Miyakawa Y: Spread times of hepatitis C virus estimated by the molecular clock differ among Japan, the United States and Egypt in reflection of their distinct socioeconomic backgrounds. Intervirology 2006;49:28-36.
35.
Pybus OG, Barnes E, Taggart R, Lemey P, Markov PV, Rasachak B, Syhavong B, Phetsouvanah R, Sheridan I, Humphreys IS, Lu L, Newton PN, Klenerman P: Genetic history of hepatitis C virus in East Asia. J Virol 2009;83:1071-1082.
36.
Drummond AJ, Ho SY, Phillips MJ, Rambaut A: Relaxed phylogenetics and dating with confidence. PLoS Biol 2006;4:e88.
37.
Kanistanon D, Neelamek M, Dharakul T, Songsivilai S: Genotypic distribution of hepatitis C virus in different regions of Thailand. J Clin Microbiol 1997;35:1772-1776.
38.
Cristina J, Colina R: Evidence of structural genomic region recombination in hepatitis C virus. Virol J 2006;3:53.
39.
Charuluxananan SC, Chentanezb V: History and evolution of Western medicine in Thailand. Asian Biomed 2007;1:5.
40.
Medhi S, Goswami B, Das AK, Singh TB, Husain SA, Sehgal A, Kar P: New insights into hepatitis C virus infection in the tribal-dominant part of northeast India. Arch Virol 2012;157:2083-2093.
41.
Hissar SS, Goyal A, Kumar M, Pandey C, Suneetha PV, Sood A, Midha V, Sakhuja P, Malhotra V, Sarin SK: Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease. J Med Virol 2006;78:452-458.
42.
Islam JH, Jamiruddin A, Ahmed R, et al.: Prevalence of hepatitis C virus genotypes in Bangladesh. 13th Annual Scientific Conference (ASCON), Dhaka, 2011, SP132, p 197.
43.
Pham DA, Leuangwutiwong P, Jittmittraphap A, Luplertlop N, Bach HK, Akkarathamrongsin S, Theamboonlers A, Poovorawan Y: High prevalence of hepatitis C virus genotype 6 in Vietnam. Asian Pac J Allergy Immunol 2009;27:153-160.
44.
Pybus OG, Rambaut A: Evolutionary analysis of the dynamics of viral infectious disease. Nat Rev Genet 2009;10:540-550.
45.
Utama A, Tania NP, Dhenni R, Gani RA, Hasan I, Sanityoso A, Lelosutan SA, Martamala R, Lesmana LA, Sulaiman A, Tai S: Genotype diversity of hepatitis C virus (HCV) in HCV-associated liver disease patients in Indonesia. Liver Int 2010;30:1152-1160.
46.
Kageyama S, Agdamag DM, Alesna ET, Abellanosa-Tac-An IP, Corpuz AC, Telan EF, Que ER, Leano PS, Jereza LD, Emphasis YE, Prasetyo AA, Tanimoto T, Ichimura H: Tracking the entry routes of hepatitis C virus as a surrogate of HIV in an HIV-low prevalence country, the Philippines. J Med Virol 2009;81:1157-1162.
47.
Liu J, Zhang C: Phylogeographic analyses reveal a crucial role of Xinjiang in HIV-1 CRF07_BC and HCV 3a transmissions in Asia. PLoS One 2011;6:e23347.
48.
Pattha P: The Impact of American Bases on Socio-Economic Condition of Udornthani, A.D. 1962-1977; thesis, Silpakorn University, Bangkok, 2007, pp 48, 61.
49.
Jittiwutikarn J, Thongsawat S, Suriyanon V, Maneekarn N, Celentano D, Razak MH, Srirak N, Vongchak T, Kawichai S, Thomas D, Sripaipan T, Netski D, Ananthakrishnan A, Nelson KE: Hepatitis C infection among drug users in northern Thailand. Am J Trop Med Hyg 2006;74:1111-1116.
50.
Chimparlee N, Oota S, Phikulsod S, Tangkijvanich P, Poovorawan Y: Hepatitis B and hepatitis C virus in Thai blood donors. Southeast Asian J Trop Med Public Health 2011;42:609-615.
51.
Buathong R: Hepatitis. Annu Epidemiol Surveill Rep 2007:88-92.
52.
Tanwandee T, Piratvisuth T, Phornphutkul K, Mairiang P, Permpikul P, Poovorawan Y: Risk factors of hepatitis C virus infection in blood donors in Thailand: a multicenter case-control study. J Med Assoc Thai 2006;89:S79-S83.
53.
Limsuwan A, Kanapa S, Siristonapun Y: Acquired immune deficiency syndrome in Thailand. A report of two cases. J Med Assoc Thai 1986;69:164-169.
54.
Attasara PB, et al: Hospital-Based Cancer Registry 2008. Bangkok, National Cancer Institute Thailand, 2009.
55.
Santayakorn S: Hepatitis. Annu Epidemiol Surveill Rep 2009;100-104.
56.
Tangkijvanich P, Mahachai V, Suwangool P, Poovorawan Y: Gender difference in clinicopathologic features and survival of patients with hepatocellular carcinoma. World J Gastroenterol 2004;10:1547-1550.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.