An integrated nationwide genomics study reveals transmission modes of typhoid fever in China
Ye Feng,
Hang Pan,
Beiwen Zheng,
Fang Li,
Lin Teng,
Zhijie Jiang,
Mengyao Feng,
Xiao Zhou,
Xianqi Peng,
Xuebin Xu,
Haoqiu Wang,
Beibei Wu,
Yonghong Xiao,
Stephen Baker,
Guoping Zhao,
Min Yue
Affiliations
Ye Feng
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
Hang Pan
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Beiwen Zheng
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, China
Fang Li
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Lin Teng
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Zhijie Jiang
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Mengyao Feng
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Xiao Zhou
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Xianqi Peng
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
Xuebin Xu
Shanghai Municipal Center for Disease Control and Prevention , Shanghai, China
Haoqiu Wang
Hangzhou Center for Disease Control and Prevention , Hangzhou, China
Beibei Wu
Zhejiang Province Center for Disease Control and Prevention , Hangzhou, China
Yonghong Xiao
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, China
Stephen Baker
University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus , Cambridge, United Kingdom
Guoping Zhao
School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences , Hangzhou, China
Min Yue
Department of Veterinary Medicine, Zhejiang University College of Animal Sciences , Hangzhou, China
ABSTRACT Typhoid fever, caused by Salmonella Typhi (S. Typhi), is a life-threatening disease, usually food-borne and commonly associated with international travel. The disease transmission remains endemic in many low- and middle-income countries, representing further hotspots for seeding new global outbreaks. China has historically been affected by typhoid fever, but the respective roles of local transmission and importation remain unknown. Here, we generated a nationwide map of the typhoid burden in China and investigated the associations between typhoid disease, climate and various socioeconomic parameters. To assess transmission dynamics, we sub-sampled S. Typhi isolated within China over five decades and sequenced their genomes. The resulting 705 new genomes, placed in context with 5,190 global isolates from 87 countries on six continents, led to the discovery of several predominant inland Chinese clones belonging to the clades 2.1/2.3/3.2/4.3. These clones were associated with multiple introductions from overseas, followed by local expansion. Notably, 4.3.1 isolates from eastern China were not genetically close to those from northwestern China but to the international isolates, indicating their association with international travel. Additional in vitro assays showed that 4.3.1 elaborated better intracellular survival, acid tolerance, and desiccation tolerance than other lineages, partially explaining its success. For the first time, we have probed typhoid transmission in China, finding local transmission and importation, which could guide the policy for typhoid control. IMPORTANCE Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network.
