Please wait a minute...

Frontiers of Medicine

Front. Med.    2014, Vol. 8 Issue (2) : 135-144
Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China
Rui Yu,Rong Fan,Jinlin Hou()
Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Download: PDF(262 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.

Keywords chronic hepatitis B      epidemiology      prevention      treatment     
Corresponding Author(s): Jinlin Hou   
Issue Date: 21 May 2014
 Cite this article:   
Jinlin Hou,Rui Yu,Rong Fan. Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China[J]. Front. Med., 2014, 8(2): 135-144.
E-mail this article
E-mail Alert
Articles by authors
Jinlin Hou
Rui Yu
Rong Fan
Fig.1  Distribution of antiviral drugs for chronic hepatitis B used in clinical practice in China. June 2012 to December 2013 (Data from 31905 patients enrolled in treatment survey in China Registry of Hepatitis B). CHB, chronic hepatitis B; NAs, nucleos(t)ide analogs. IFNs, interferons; LAM, lamivudine; ETV, entecavir; ADV, adefovir; TDF, tenofovir; LDT, telbivudine. a including hepatic protectant, immunomodulator, traditional Chinese medicine and drugs unknown.
Nucleos(t)ide analogsLamivudineAdefovirTelbivudineEntecavirTenofovir
Duration (year)35554b4b3577
HBV DNA<300–400 copies/ml (%)40NA533986.476.298949999
HBeAg seroconversion (%)/44a/30/53.2/23/40
HBsAg loss (%)NANA520.61.9NA1.4NA12
HBV resistance (%)NA71292015.918.81.2c00
Tab.1  Latest results of major clinical studies on the efficacy and drug- resistance of nucleos(t)ide analogs
Fig.2  Response-guided therapy for pegylated interferon treatment in patients with chronic hepatitis B.
1 World Health Organization. Hepatitis B. (Revised July 2013). [2010–11–<day>30</day>]
2 GanemD, PrinceAM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med2004; 350(11): 1118–1129
doi: 10.1056/NEJMra031087 pmid: 15014185
3 ChanHL, SungJJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis2006; 26(2): 153–161
doi: 10.1055/s-2006-939753 pmid: 16673293
4 LiangX, BiS, YangW, WangL, CuiG, CuiF, ZhangY, LiuJ, GongX, ChenY, WangF, ZhengH, WangF, GuoJ, JiaZ, MaJ, WangH, LuoH, LiL, JinS, HadlerSC, WangY. Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine2009; 27(47): 6550–6557
doi: 10.1016/j.vaccine.2009.08.048 pmid: 19729084
5 SchaeferS. Hepatitis B virus: significance of genotypes. J Viral Hepat2005; 12(2): 111–124
doi: 10.1111/j.1365-2893.2005.00584.x pmid: 15720525
6 ZengG, WangZ, WenS, JiangJ, WangL, ChengJ, TanD, XiaoF, MaS, LiW, LuoK, NaoumovNV, HouJ. Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. J Viral Hepat2005; 12(6): 609–617
doi: 10.1111/j.1365-2893.2005.00657.x pmid: 16255762
7 WangZ, LiuZ, ZengG, WenS, QiY, MaS, NaoumovNV, HouJ. A new intertype recombinant between genotypes C and D of hepatitis B virus identified in China. J Gen Virol2005; 86(Pt 4): 985–990
doi: 10.1099/vir.0.80771-0 pmid: 15784891
8 ZhouB, XiaoL, WangZ, ChangET, ChenJ, HouJ. Geographical and ethnic distribution of the HBV C/D recombinant on the Qinghai-Tibet Plateau. PLoS One2011; 6(4): e18708
doi: 10.1371/journal.pone.0018708 pmid: 21494570
9 ZhouB, WangZ, YangJ, SunJ, LiH, TanakaY, MizokamiM, HouJ. Novel evidence of HBV recombination in family cluster infections in western China. PLoS One2012; 7(6): e38241
doi: 10.1371/journal.pone.0038241 pmid: 22675528
10 ChenCJ, YangHI, SuJ, JenCL, YouSL, LuSN, HuangGT, IloejeUH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA2006; 295(1): 65–73
doi: 10.1001/jama.295.1.65 pmid: 16391218
11 European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol2012; 57(1): 167–185
pmid: 22436845
12 LiawYF, KaoJH, PiratvisuthT, ChanH, ChienRN, LiuCJ, GaneE, LocarniniS, LimSG, HanKH, AmarapurkarD, CooksleyG, JafriW, MohamedR, HouJL, ChuangWL, LesmanaL, SollanoJ, SuhDJ, OmataM. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatology International2012; 6(3): 531–561
doi: 10.1007/s12072-012-9365-4
13 LokAS, McMahonBJ. Chronic hepatitis B: update 2009. Hepatology2009; 50(3): 661–662
doi: 10.1002/hep.23190 pmid: 19714720
14 SonneveldMJ, HansenBE, PiratvisuthT, JiaJD, ZeuzemS, GaneE, LiawYF, XieQ, HeathcoteEJ, ChanHL, JanssenHL. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels. Hepatology2013; 58(3): 872–880
doi: 10.1002/hep.26436 pmid: 23553752
15 HouJ, MaH, SunJ, XieQ, XieY, SunY, WangH, ShiG, WanM, NiuJ, NingQ, YuY, ZhaoY. Response guided peginterferon alfa-2a (PegIFN alfa-2a) therapy in patients with HBeAg-positive chronic hepatitis B (CHB). J Hepatol2014[Epub ahead of print] (abstract)
16 RijckborstV, HansenBE, CakalogluY, FerenciP, TabakF, AkdoganM, SimonK, AkarcaUS, FlisiakR, VerheyE, Van VuurenAJ, BoucherCA, ter BorgMJ, JanssenHL. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology2010; 52(2): 454–461
doi: 10.1002/hep.23722 pmid: 20683945
17 NingQ, HanM, SunY, JiangJJ, TanD, HouJ, TangH, ShengJF, JiangM. Patients with HBeAg-positive chronic hepatitis B (CHB) with a maintained virological response to entecavir achieved HBsAg clearance when switched to peginterferon alfa-2a therapy (the OSST study). Hepatology2011; 54(Suppl): 1010–1A
18 ChanHL. Peginterferon therapy for chronic hepatitis B: one size fits all? Gut2013; 62(2): 185–187
doi: 10.1136/gutjnl-2012-303291 pmid: 22942237
19 TenneyDJ, PokornowskiKA, RoseRE, BaldickCJ, EggersBJ, FangJ, WichroskiMJ, DivaUA, XuD, WilberRB, Brett-SmithH, IloejeUH. 20 entecavir maintains a high genetic barrier to HBV resistance through 6 years in naive patients. J Hepatol2009; 50(Suppl): S10
doi: 10.1016/S0168-8278(09)60022-2
20 YokosukaO, TakaguchiK, FujiokaS, ShindoM, ChayamaK, KobashiH, HayashiN, SatoC, KiyosawaK, TanikawaK, IshikawaH, MasakiN, SeriuT, OmataM. Long-term use of entecavir in nucleoside-naïve Japanese patients with chronic hepatitis B infection. J Hepatol2010; 52(6): 791–799
doi: 10.1016/j.jhep.2009.12.036 pmid: 20409606
21 MarcellinEJGP, TsaiN, FlisiakR, PetersenSGJ, KotzevIA, FlahertyJF, DinhP, GaggarA, KitrinosKM, SubramanianM, McHutchisonJG, GeorgeJ, ButiM. Seven years of treatment with tenofovir DF for chronic hepatitis B virus infection is safe and well tolerated and associated with sustained virological, biochemical and serological responses with no detectable resistance. Hepatology2013; 58(S1): 649A
22 MarcellinP, GaneE, ButiM, AfdhalN, SievertW, JacobsonIM, WashingtonMK, GermanidisG, FlahertyJF, SchallRA, BornsteinJD, KitrinosKM, SubramanianGM, McHutchisonJG, HeathcoteEJ. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet2013; 381(9865): 468–475
doi: 10.1016/S0140-6736(12)61425-1 pmid: 23234725
23 LokAS, LaiCL, LeungN, YaoGB, CuiZY, SchiffER, DienstagJL, HeathcoteEJ, LittleNR, GriffithsDA, GardnerSD, CastigliaM. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology2003; 125(6): 1714–1722
doi: 10.1053/j.gastro.2003.09.033 pmid: 14724824
24 HadziyannisSJ, TassopoulosNC, HeathcoteEJ, ChangTT, KitisG, RizzettoM, MarcellinP, LimSG, GoodmanZ, MaJ, BrosgartCL, Borroto-EsodaK, ArterburnS, Chuck SL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology2006; 131(6): 1743–1751
doi: 10.1053/j.gastro.2006.09.020 pmid: 17087951
25 YuenMF, SablonE, HuiCK, YuanHJ, DecraemerH, LaiCL. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. Hepatology2001; 34(4): 785–791
26 ChaeHB, HannHW, HuiCK, YuanHJ, DecraemerH, LaiCL. Baseline HBV DNA level is the most important factor associated with virologic breakthrough in chronic hepatitis B treated with lamivudine. World J Gastroenterol2007; 13(30): 4085–4090
pmid: 17696226
27 LiawYF, GaneE, LeungN, ZeuzemS, WangY, LaiCL, HeathcoteEJ, MannsM, BzowejN, NiuJ, HanSH, HwangSG, CakalogluY, TongMJ, PapatheodoridisG, ChenY, BrownNA, AlbanisE, GalilK, NaoumovNV; GLOBE Study Group. 2-Year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology2009; 136(2): 486–495
doi: 10.1053/j.gastro.2008.10.026 pmid: 19027013
28 HannHW. Telbivudine: an effective anti-HBV drug for chronic hepatitis B patients with early on-treatment responses. Expert Opin Pharmacother2010; 11(13): 2243–2249
doi: 10.1517/14656566.2010.512437 pmid: 20698726
29 SungJJ, LaiJY, ZeuzemS, ChowWC, HeathcoteEJ, PerrilloRP, BrosgartCL, WoessnerMA, ScottSA, GrayDF, GardnerSD. Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B. J Hepatol2008; 48(5): 728–735
doi: 10.1016/j.jhep.2007.12.026 pmid: 18329126
30 HuiCK, ZhangHY, BowdenS, LocarniniS, LukJM, LeungKW, YuengYH, WongA, RousseauF, YuenKY, NaoumovNN, LauGK. 96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B. J Hepatol2008; 48(5): 714–720
doi: 10.1016/j.jhep.2007.10.013 pmid: 18207280
31 LokAS1, TrinhH, CarosiG, AkarcaUS, GadanoA, HabersetzerF, SievertW, WongD, LovegrenM, CohenD, LlamosoC. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naive patients with chronic hepatitis B. Gastroenterology2012; 143(3): 619–28 e1
pmid: 22643350
32 TerraultNA. Benefits and risks of combination therapy for hepatitis B. Hepatology2009; 49(5 Suppl): S122–S128
doi: 10.1002/hep.22921 pmid: 19399796
33 KeeffeEB, ZeuzemS, KoffRS, DieterichDT, Esteban-MurR, GaneEJ, JacobsonIM, LimSG, NaoumovN, MarcellinP, PiratvisuthT, ZoulimF. Report of an international workshop: roadmap for management of patients receiving oral therapy for chronic hepatitis B. Clin Gastroenterol Hepatol2007; 5(8): 890–897
doi: 10.1016/j.cgh.2007.05.004 pmid: 17632041
34 SunJ, XieQ, TanD, NingQ, NiuJ, BaiX, FanR, ChenS, ChengJ, YuY, WangH, XuM, ShiG, WanM, ChenX, TangH, ShengJ, DouX, ShiJ, RenH, WangM, ZhangH, GaoZ, ChenC, MaH, JiaJ, HouJ. The 104-week efficacy and safety of telbivudine-based optimization strategy in chronic hepatitis B patients: a randomized, controlled study. Hepatology2014; 59(4): 1283–1292
pmid: 24382690
35 PetersMG, Hann HwHw, MartinP, HeathcoteEJ, BuggischP, RubinR, BourliereM, KowdleyK, TrepoC, Gray DfDf, SullivanM, KleberK, EbrahimiR, XiongS, BrosgartCL. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology2004; 126(1): 91–101
doi: 10.1053/j.gastro.2003.10.051 pmid: 14699491
36 RaptiI, DimouE, MitsoulaP, HadziyannisSJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology2007; 45(2): 307–313
doi: 10.1002/hep.21534 pmid: 17256746
37 LamperticoP, ViganòM, ManentiE, IavaroneM, SablonE, ColomboM. Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients. Gastroenterology2007; 133(5): 1445–1451
doi: 10.1053/j.gastro.2007.08.079 pmid: 17983801
38 YangH, QiX, SabogalA, MillerM, XiongS, DelaneyWE 4th. Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV. Antivir Ther2005; 10(5): 625–633
pmid: 16152756
39 LadaO, BenhamouY, CahourA, KatlamaC, PoynardT, ThibaultV. In vitro susceptibility of lamivudine-resistant hepatitis B virus to adefovir and tenofovir. Antivir Ther2004; 9(3): 353–363
pmid: 15259898
40 SunJ, HouJL, XieQ, LiXH, ZhangJM, WangYM, WangH, LaiJY, ChenSJ, JiaJD, ShengJF, ChanHL, WangJF, LiMK, JiangM, PopescuM, SungJJ. Randomised clinical trial: efficacy of peginterferon alfa-2a in HBeAg positive chronic hepatitis B patients with lamivudine resistance. Aliment Pharmacol Ther2011; 34(4): 424–431
doi: 10.1111/j.1365-2036.2011.04750.x pmid: 21692822
41 BergT, MarcellinP, ZoulimF, MollerB, TrinhH, ChanS, SuarezE, LavocatF, Snow-LampartA, FrederickD, SorbelJ, Borroto-EsodaK, OldachD, RousseauF. Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection. Gastroenterology2010; 139(4): 1207–1217, e3
doi: 10.1053/j.gastro.2010.06.053 pmid: 20600025
42 ShermanM, YurdaydinC, SollanoJ, SilvaM, LiawYF, CianciaraJ, Boron-KaczmarskaA, MartinP, GoodmanZ, ColonnoR, CrossA, DeniskyG, KreterB, HindesR; AI463026 BEHoLD Study Group. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology2006; 130(7): 2039–2049
doi: 10.1053/j.gastro.2006.04.007 pmid: 16762627
43 ShermanM, YurdaydinC, SimsekH, SilvaM, LiawYF, RustgiVK, SetteH, TsaiN, TenneyDJ, VaughanJ, KreterB, HindesR; AI463026 Benefits of Entecavir for Hepatitis B Liver Disease (BEHoLD) Study Group. Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical, and serology outcomes through 96 weeks. Hepatology2008; 48(1): 99–108
doi: 10.1002/hep.22323 pmid: 18537189
44 PetersenJ, RatziuV, ButiM, JanssenHL, BrownA, LamperticoP, SchollmeyerJ, ZoulimF, WedemeyerH, SterneckM, BergT, SarrazinC, LutgehetmannM, BuggischP. Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: an international multicenter cohort study. J Hepatol2012; 56(3): 520–526
doi: 10.1016/j.jhep.2011.09.018 pmid: 22037226
45 ChotiyaputtaW, PetersonC, DitahFA, GoodwinD, LokAS. Persistence and adherence to nucleos(t)ide analogue treatment for chronic hepatitis B. J Hepatol2011; 54(1): 12–18
doi: 10.1016/j.jhep.2010.06.016 pmid: 20888661
46 DomingoE. Viruses at the edge of adaptation. Virology2000; 270(2): 251–253
doi: 10.1006/viro.2000.0320 pmid: 10792982
47 RodriguezC, ChevaliezS, BensadounP, PawlotskyJM. Characterization of the dynamics of hepatitis B virus resistance to adefovir by ultra-deep pyrosequencing. Hepatology2013; 58(3): 890–901
doi: 10.1002/hep.26383 pmid: 23505208
48 MaSW, HuangX, LiYY, TangLB, SunXF, JiangXT, ZhangYX, SunJ, LiuZH, AbbottWG, DongYH, NaoumovNV, HouJL. High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B. J Hepatol2012; 56(4): 775–781
doi: 10.1016/j.jhep.2011.10.020 pmid: 22173154
49 LiY, MaS, TangL, LiY, WangW, HuangX, LaiQ, ZhangM, SunJ, LiCK, AbbottWG, NaoumovNV, ZhangY, HouJ. Circulating chemokine (C-X-C Motif) receptor 5(+) CD4(+) T cells benefit hepatitis B e antigen seroconversion through IL-21 in patients with chronic hepatitis B virus infection. Hepatology2013; 58(4): 1277–1286
doi: 10.1002/hep.26489 pmid: 23703545
50 WongVW, ChanHL. Transient elastography. J Gastroenterol Hepatol2010; 25(11): 1726–1731
doi: 10.1111/j.1440-1746.2010.06437.x pmid: 21039833
51 ChanHL, WongGL, ChoiPC, ChanAW, ChimAM, YiuKK, ChanFK, SungJJ, WongVW. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat2009; 16(1): 36–44
doi: 10.1111/j.1365-2893.2008.01037.x pmid: 18673426
52 ChenYP, LiangXE, DaiL, ZhangQ, PengJ, ZhuYF, WenWQ, ChanHL, HouJL. Improving transient elastography performance for detecting hepatitis B cirrhosis. Dig Liver Dis2012; 44(1): 61–66
doi: 10.1016/j.dld.2011.08.004 pmid: 21907650
53 ChenYP, ZhangQ, DaiL, LiangXE, PengJ, HouJL. Is transient elastography valuable for high-risk esophageal varices prediction in patients with hepatitis-B-related cirrhosis? J Gastroenterol Hepatol2012; 27(3): 533–539
doi: 10.1111/j.1440-1746.2011.06889.x pmid: 21871027
Related articles from Frontiers Journals
[1] Ke Sheng. Artificial intelligence in radiotherapy: a technological review[J]. Front. Med., 2020, 14(4): 431-449.
[2] Cenyi Shao, Shijian Li, Feng Zhu, Dahai Zhao, Hui Shao, Haixiao Chen, Zhiruo Zhang. Taizhou’s COVID-19 prevention and control experience with telemedicine features[J]. Front. Med., 2020, 14(4): 506-510.
[3] Min Zhou, Xinxin Zhang, Jieming Qu. Coronavirus disease 2019 (COVID-19): a clinical update[J]. Front. Med., 2020, 14(2): 126-135.
[4] Honglu Zhou, Songmei Wang, Lorenz von Seidlein, Xuanyi Wang. The epidemiology of norovirus gastroenteritis in China: disease burden and distribution of genotypes[J]. Front. Med., 2020, 14(1): 1-7.
[5] Xiaoxin Wu, Lanlan Xiao, Lanjuan Li. Research progress on human infection with avian influenza H7N9[J]. Front. Med., 2020, 14(1): 8-20.
[6] Tung Huynh, Ke-Qin Hu. Direct acting antiviral-induced dynamic reduction of serum α fetoprotein in hepatitis C patients without hepatocellular carcinoma[J]. Front. Med., 2019, 13(6): 658-666.
[7] Tianyuan Li, Renbing Jia, Xianqun Fan. Classification and treatment of orbital venous malformations: an updated review[J]. Front. Med., 2019, 13(5): 547-555.
[8] Jing Yue, Bo Zhang, Mingyue Wang, Junning Yao, Yifan Zhou, Ding Ma, Lei Jin. Effect of antitubercular treatment on the pregnancy outcomes and prognoses of patients with genital tuberculosis[J]. Front. Med., 2019, 13(1): 121-125.
[9] Eun Young Lee, Kun-Ho Yoon. Epidemic obesity in children and adolescents: risk factors and prevention[J]. Front. Med., 2018, 12(6): 658-666.
[10] Minhong Shen, Yibin Kang. Complex interplay between tumor microenvironment and cancer therapy[J]. Front. Med., 2018, 12(4): 426-439.
[11] Kuo Yang, Runshun Zhang, Liyun He, Yubing Li, Wenwen Liu, Changhe Yu, Yanhong Zhang, Xinlong Li, Yan Liu, Weiming Xu, Xuezhong Zhou, Baoyan Liu. Multistage analysis method for detection of effective herb prescription from clinical data[J]. Front. Med., 2018, 12(2): 206-217.
[12] Chongguang Yang, Qian Gao. Recent transmission of Mycobacterium tuberculosis in China: the implication of molecular epidemiology for tuberculosis control[J]. Front. Med., 2018, 12(1): 76-83.
[13] Min Chen, Yuan Xu, Nan Hong, Yali Yang, Wenzhi Lei, Lin Du, Jingjun Zhao, Xia Lei, Lin Xiong, Langqi Cai, Hui Xu, Weihua Pan, Wanqing Liao. Epidemiology of fungal infections in China[J]. Front. Med., 2018, 12(1): 58-75.
[14] Qingmeng Zhang, Fengmin Zhang, Baofeng Yang. Pneumonic plague epidemic in Northeast China in 1910–1911: Dr. Wu Lien-Teh’s epidemic preventive system for plague control[J]. Front. Med., 2018, 12(1): 113-115.
[15] Biao Kan, Haijian Zhou, Pengcheng Du, Wen Zhang, Xin Lu, Tian Qin, Jianguo Xu. Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the trace[J]. Front. Med., 2018, 12(1): 23-33.
Full text