Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

2015 Impact Factor: 1.863

Cover Story   2018, Volume 12 Issue 1
The infectious outbreaks have largely been investigated with both of the principles established by John Snow in 1854 and the recent developed methodology known as genome epidemiology. (Courtesy of Dr. Biao Kan. See pages 23?33 by Biao Kan et al. for more information.)
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EDITORIAL
REVIEW
Landscape of emerging and re-emerging infectious diseases in China: impact of ecology, climate, and behavior
Qiyong Liu, Wenbo Xu, Shan Lu, Jiafu Jiang, Jieping Zhou, Zhujun Shao, Xiaobo Liu, Lei Xu, Yanwen Xiong, Han Zheng, Sun Jin, Hai Jiang, Wuchun Cao, Jianguo Xu
Front. Med.. 2018, 12 (1): 3-22.  
https://doi.org/10.1007/s11684-017-0605-9

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For the past several decades, the infectious disease profile in China has been shifting with rapid developments in social and economic aspects, environment, quality of food, water, housing, and public health infrastructure. Notably, 5 notifiable infectious diseases have been almost eradicated, and the incidence of 18 additional notifiable infectious diseases has been significantly reduced. Unexpectedly, the incidence of over 10 notifiable infectious diseases, including HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless, frequent infectious disease outbreaks/events have been reported almost every year, and imported infectious diseases have increased since 2015. New pathogens and over 100 new genotypes or serotypes of known pathogens have been identified. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests. This review summarizes the current experiences and lessons from China in managing emerging and re-emerging infectious diseases, especially the effects of ecology, climate, and behavior, which should have merits in helping other countries to control and prevent infectious diseases.

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Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the trace
Biao Kan, Haijian Zhou, Pengcheng Du, Wen Zhang, Xin Lu, Tian Qin, Jianguo Xu
Front. Med.. 2018, 12 (1): 23-33.  
https://doi.org/10.1007/s11684-017-0607-7

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Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.

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Innate and adaptive T cells in influenza disease
Simone Nüssing, Sneha Sant, Marios Koutsakos, Kanta Subbarao, Thi H.O. Nguyen, Katherine Kedzierska
Front. Med.. 2018, 12 (1): 34-47.  
https://doi.org/10.1007/s11684-017-0606-8

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Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8+ and CD4+ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

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Trends of foodborne diseases in China: lessons from laboratory-based surveillance since 2011
Jikai Liu, Li Bai, Weiwei Li, Haihong Han, Ping Fu, Xiaochen Ma, Zhenwang Bi, Xiaorong Yang, Xiuli Zhang, Shiqi Zhen, Xiaoling Deng, Xiumei Liu, Yunchang Guo
Front. Med.. 2018, 12 (1): 48-57.  
https://doi.org/10.1007/s11684-017-0608-6

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Foodborne disease is one of the most important public health issues worldwide. China faces various and unprecedented challenges in all aspects of the food chain. Data from laboratory-based foodborne disease surveillance systems from 2013 to 2016, as well as different regions and ages, can be found along with differences in the patterns of pathogens detected with diverse characteristics. Vibrio parahaemolyticus has been the leading cause of infectious diarrhea in China, especially among adults in coastal regions. Salmonella has been a serious and widely distributed pathogen responsible for substantial socioeconomic burden. Shigella was mostly identified in Northwest China and the inland province (Henan) with less-developed regions among children under 5 years. Data from foodborne disease outbreak reporting system from 2011 to 2016 showed that poisonous animals and plant factors responsible for most deaths were poisonous mushrooms (54.7%) in remote districts in southwest regions. The biological hazard that caused most cases reported (42.3%) was attributed to V. parahaemolyticus, the leading cause of foodborne outbreaks. In this review, we summarize the recent monitoring approach to foodborne diseases in China and compare the results with those in developed countries.

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Epidemiology of fungal infections in China
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
Front. Med.. 2018, 12 (1): 58-75.  
https://doi.org/10.1007/s11684-017-0601-0

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With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillus fumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country’s health.

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Recent transmission of Mycobacterium tuberculosis in China: the implication of molecular epidemiology for tuberculosis control
Chongguang Yang, Qian Gao
Front. Med.. 2018, 12 (1): 76-83.  
https://doi.org/10.1007/s11684-017-0609-5

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Tuberculosis (TB) has remained an ongoing concern in China. The national scale-up of the Directly Observed Treatment, Short Course (DOTS) program has accelerated the fight against TB in China. Nevertheless, many challenges still remain, including the spread of drug-resistant strains, high disease burden in rural areas, and enormous rural-to-urban migrations. Whether incident active TB represents recent transmission or endogenous reactivation has helped to prioritize the strategies for TB control. Evidence from molecular epidemiology studies has delineated the recent transmission of Mycobacterium tuberculosis (M. tuberculosis) strains in many settings. However, the transmission patterns of TB in most areas of China are still not clear. Studies carried out to date could not capture the real burden of recent transmission of the disease in China because of the retrospective study design, incomplete sampling, and use of low-resolution genotyping methods. We reviewed the implementations of molecular epidemiology of TB in China, the estimated disease burden due to recent transmission of M. tuberculosis strains, the primary transmission of drug-resistant TB, and the evaluation of a feasible genotyping method of M. tuberculosis strains in circulation.

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RESEARCH ARTICLE
Etiology of invasive candidosis agents in Russia: a multicenter epidemiological survey
N.V. Vasilyeva, E.R. Raush, M.V. Rudneva, T.S. Bogomolova, A.E. Taraskina, Yong Fang, Fengmin Zhang, N.N. Klimko
Front. Med.. 2018, 12 (1): 84-91.  
https://doi.org/10.1007/s11684-017-0612-x

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A multicenter prospective epidemiological survey on the etiologic agents of invasive candidosis was conducted in Russia in the period of 2012–2014. Samples were collected from 284 patients with invasive candidosis and Candida species isolated by culture. The species were identified by DNA sequencing and MALDI-TOF mass-spectrometry. A total of 322 isolates were recovered, in which 96% of Сandida species belonged to six major species, namely, C. albicans (43.2%), C. parapsilosis (20.2%), C. glabrata (11.5%), C. tropicalis (9.6%), C. krusei (6.2%), and C. guilliermondii (5.3%). Most Candida species were isolated from blood samples (83.23%). Notably, the prevalence rate of C. albicans reduced from 52.38% to 32.79% (2012 vs. 2014) (P=0.01) whereas that of non-C. albicans increased from 47.62% (2012) to 67.21% (2014) (P<0.01). Species distribution differed among geographical regions; specifically, the prevalence rate of C. albicans as an etiologic agent of invasive candidosis in Siberian Federal region was significantly higher than that in other Federal regions. Results indicated a shift from C. albicans to non-C. albicans. Therefore, a detailed investigation on the contributing factors and appropriate treatment of invasive candidosis is needed.

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Associations between Mycobacterium tuberculosis Beijing genotype and drug resistance to four first-line drugs: a survey in China
Haican Liu, Yuanyuan Zhang, Zhiguang Liu, Jinghua Liu, Yolande Hauck, Jiao Liu, Haiyan Dong, Jie Liu, Xiuqin Zhao, Bing Lu, Yi Jiang, Gilles Vergnaud, Christine Pourcel, Kanglin Wan
Front. Med.. 2018, 12 (1): 92-97.  
https://doi.org/10.1007/s11684-017-0610-z

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Investigations on the genetic diversity of Mycobacterium tuberculosis in China have shown that Beijing genotype strains play a dominant role. To study the association between the M.?tuberculosis Beijing genotype and the drug-resistance phenotype, 1286 M. tuberculosis clinical isolates together with epidemiological and clinical information of patients were collected from the center for tuberculosis (TB) prevention and control or TB hospitals in Beijing municipality and nine provinces or autonomous regions in China. Drug resistance testing was conducted on all the isolates to the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin, and ethambutol). A total of 585 strains were found to be resistant to at least one of the four anti-TB drugs. The Beijing family strains consisted of 499 (53.20%) drug-sensitive strains and 439 (46.80%) drug-resistant strains, whereas the non-Beijing family strains comprised 202 (58.05%) drug-sensitive strains and 146 (41.95%) drug-resistant strains. No significant difference was observed in prevalence (c2=2.41, P>0.05) between the drug-resistant and drug-sensitive strains among the Beijing family strains. Analysis of monoresistance, multidrug-resistant TB, and geographic distribution of drug resistance did not find any relationships between the M.?tuberculosis Beijing genotype and drug-resistance phenotype in China. Results confirmed that the Beijing genotype, the predominant M. tuberculosis genotype in China, was not associated with drug resistance.

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Cyclospora cayetanensis infections among diarrheal outpatients in Shanghai: a retrospective case study
Yanyan Jiang, Zhongying Yuan, Guoqing Zang, Dan Li, Ying Wang, Yi Zhang, Hua Liu, Jianping Cao, Yujuan Shen
Front. Med.. 2018, 12 (1): 98-103.  
https://doi.org/10.1007/s11684-018-0614-3

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Cyclospora cayetanensis is a foodborne and waterborne pathogen that causes endemic and epidemic human diarrhea worldwide. A few epidemiological studies regarding C. cayetanensis infections in China have been conducted. During 2013, a total of 291 stool specimens were collected from patients with diarrhea at a hospital in urban Shanghai. C. cayetanensis was not detected in any of the stool specimens by traditional microscopy, whereas five stool specimens (1.72%, 5/291) were positive by PCR. These positive cases confirmed by molecular technology were all in the adult group (mean age 27.8 years; 2.94%, 5/170) with watery diarrhea. Marked infection occurred in the rainy season of May and July. Sequence and phylogenetic analyses of the partial 18S rRNA genes of C. cayetanensis isolated showed intra-species diversity of this parasite. This study showed, for the first time, that C. cayetanensis is a pathogen in outpatients with diarrhea in Shanghai, albeit at a low level. However, the transmission dynamics of this parasite in these patients remain uncertain.

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Prevalence and molecular characteristics of Listeria monocytogenes in cooked products and its comparison with isolates from listeriosis cases
Hong Wang, Lijuan Luo, Zhengdong Zhang, Jianping Deng, Yan Wang, Yimao Miao, Ling Zhang, Xi Chen, Xiang Liu, Songsong Sun, Bo Xiao, Qun Li, Changyun Ye
Front. Med.. 2018, 12 (1): 104-112.  
https://doi.org/10.1007/s11684-017-0593-9

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This study aimed to investigate the prevalence and molecular characteristics of Listeria monocytogenes in cooked products in Zigong City, China. The overall occurrence of the L. monocytogenes in the ready-to-eat (RTE) shops and mutton restaurants surveyed was 16.2% (141/873). An occurrence of 13.5% was observed in RTE pork, 6.5% in RTE vegetables, and more than 24.0% in either cooked mutton or cooked haggis. Serotype 1/2b (45.4%), 1/2a (33.3%), and 1/2c (14.2%) were the predominant types. By comparing the clonal complexes (CCs) based on multilocus sequence typing (MLST) of the L. monocytogenes from cooked foods in Zigong City and 33 listeriosis cases from different districts of China, CC87, CC9, CC8, and CC3 were showed to be prevalent in cooked products and CC87 and CC3 were the first two frequent types in the 33 clinic-source strains. All CC87 stains harbored the newly reported Listeria pathogenicity island 4 (LIPI-4) gene fragment ptsA, and all CC3 strains possessed the Listeria pathogenicity island 3 (LIPI-3) gene fragment llsX. These may increase the occurrence of the strains belonging to CC87 and CC3 in listeriosis cases in China and also underline the risk of infection owing to the consumption of the cooked products from Zigong. ST619 (serotype 1/2b) harbored both llsX and ptsA, indicating a potential hypervirulent sequence type in Zigong.

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COMMENTARY
Pneumonic plague epidemic in Northeast China in 1910–1911: Dr. Wu Lien-Teh’s epidemic preventive system for plague control
Qingmeng Zhang, Fengmin Zhang, Baofeng Yang
Front. Med.. 2018, 12 (1): 113-115.  
https://doi.org/10.1007/s11684-018-0613-4

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Pneumonic plague that originated in Russian Siberia broke out in Northeast China in October 1910–March 1911. On the basis of field visits, autopsy, bacteriological identification, and close collaboration with local authorities and international colleagues, Dr. Wu Lien-Teh implemented a series of efficient antiplague measures, which successfully controlled the development of an extraordinary epidemic plague. In his subsequent work, Dr. Wu demonstrated the respiratory transmission of pneumonic plague and tarbagans’ role in this spread. Dr. Wu’s academic and cultural contributions are valuable in the medical progress in China.

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Low-dose CT for lung cancer screening: opportunities and challenges
Hongbing Shen
Front. Med.. 2018, 12 (1): 116-121.  
https://doi.org/10.1007/s11684-017-0600-1

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Lung cancer is among the most frequently diagnosed cancers worldwide and the leading cause of cancer death in both males and females. Screening for lung cancer coupled with earlier intervention has long been studied as an approach to mortality reduction. However, minimal progress was achieved until recently, when low-dose spiral computed tomography (LDCT) screening demonstrated a 20% reduction in mortality from lung cancer in a randomized controlled trial (RCT), the National Lung Screening Trial, from the United States. On the basis of this finding, LDCT has been recommended for lung cancer screening in high-risk populations by several clinical guidelines. However, results from the following independent RCTs in Europe failed to show consistent conclusions. In addition, intractable problems gradually emerged with the progress of LDCT screening. This paper summarizes and discusses the main observations and challenges of LDCT screening for lung cancer. Before spreading implementation of LDCT screening, challenges, including high false-positive rates, overdiagnosis, enormous costs, and radiation risk, must be addressed. Complementary biomarkers and technical improvement are expected in the field of lung cancer screening in the near future.

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13 articles