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      A Large-Scale Community-Based Outbreak of Paratyphoid Fever Caused by Hospital-Derived Transmission in Southern China

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          Abstract

          Background

          Since the 1990s, paratyphoid fever caused by Salmonella Paratyphi A has emerged in Southeast Asia and China. In 2010, a large-scale outbreak involving 601 cases of paratyphoid fever occurred in the whole of Yuanjiang county in China. Epidemiological and laboratory investigations were conducted to determine the etiology, source and transmission factors of the outbreak.

          Methodology/Principal Findings

          A case-control study was performed to identify the risk factors for this paratyphoid outbreak. Cases were identified as patients with blood culture–confirmed S. Paratyphi A infection. Controls were healthy persons without fever within the past month and matched to cases by age, gender and geography. Pulsed-field gel electrophoresis and whole-genome sequencing of the S. Paratyphi A strains isolated from patients and environmental sources were performed to facilitate transmission analysis and source tracking. We found that farmers and young adults were the populations mainly affected in this outbreak, and the consumption of raw vegetables was the main risk factor associated with paratyphoid fever. Molecular subtyping and genome sequencing of S. Paratyphi A isolates recovered from improperly disinfected hospital wastewater showed indistinguishable patterns matching most of the isolates from the cases. An investigation showed that hospital wastewater mixed with surface water was used for crop irrigation, promoting a cycle of contamination. After prohibition of the planting of vegetables in contaminated fields and the thorough disinfection of hospital wastewater, the outbreak subsided. Further analysis of the isolates indicated that the origin of the outbreak was most likely from patients outside Yuanjiang county.

          Conclusions

          This outbreak is an example of the combined effect of social behaviors, prevailing ecological conditions and improper disinfection of hospital wastewater on facilitating a sustained epidemic of paratyphoid fever. This study underscores the critical need for strict treatment measures of hospital wastewater and the maintenance of independent agricultural irrigation systems in rural areas.

          Author Summary

          Typhoid and paratyphoid fever remain public health concerns for developing countries. From May 2010 to June 2011, a large-scale outbreak involving 601 cases of paratyphoid fever occurred in China. Epidemiological and laboratory investigations were conducted to determine the etiology, source and transmission factors of the outbreak. Farmers and young adults were the populations mainly affected in this outbreak, and the consumption of raw vegetables was the main risk factor associated with paratyphoid fever. We found that hospital wastewater mixed with surface water was used for vegetable irrigation. The contaminated water from hospitals combined with the regional habit of eating uncooked vegetables lead to the massive outbreak of paratyphoid. After prohibition of the planting of vegetables in contaminated fields and the thorough disinfection of hospital wastewater, the outbreak subsided. Molecular subtyping and whole-genome sequencing of S. Paratyphi A isolates recovered from improperly disinfected hospital wastewater showed indistinguishable patterns matching most of the isolates from the cases. Further analysis of the isolates indicated that the origin of the outbreak was most likely from patients outside Yuanjiang county. This study underscores the critical need for strict treatment measures of hospital wastewater and the maintenance of independent agricultural irrigation systems in rural areas.

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          Most cited references17

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          PulseNet: the molecular subtyping network for foodborne bacterial disease surveillance, United States.

          PulseNet, the national molecular subtyping network for foodborne disease surveillance, was established by the Centers for Disease Control and Prevention and several state health department laboratories to facilitate subtyping bacterial foodborne pathogens for epidemiologic purposes. PulseNet, which began in 1996 with 10 laboratories typing a single pathogen (Escherichia coli O157:H7), now includes 46 state and 2 local public health laboratories and the food safety laboratories of the U.S. Food and Drug Administration and the U.S. Department of Agriculture. Four foodborne pathogens (E. coli O157:H7; nontyphoidal Salmonella serotypes, Listeria monocytogenes and Shigella) are being subtyped, and other bacterial, viral, and parasitic organisms will be added soon.
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            Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010

            Background Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies. Methods We conducted a systematic literature review of the PubMed and Scopus databases using pre-defined criteria to identify population-based studies with typhoid fever incidence data published between 1980 and 2009. We also abstracted data from annual reports of notifiable diseases in countries with advanced surveillance systems. Typhoid and paratyphoid fever input data were grouped into regions and regional incidence and mortality rates were estimated. Incidence data were extrapolated across regions for those lacking data. Age-specific incidence rates were derived for regions where age-specific data were available. Crude and adjusted estimates of the global typhoid fever burden were calculated. Results Twenty-five studies were identified, all of which contained incidence data on typhoid fever and 12 on paratyphoid fever. Five advanced surveillance systems contributed data on typhoid fever; 2 on paratyphoid fever. Regional typhoid fever incidence rates ranged from <0.1/100 000 cases/y in Central and Eastern Europe and Central Asia to 724.6/100 000 cases/y in Sub-Saharan Africa. Regional paratyphoid incidence rates ranged from 0.8/100 000 cases/y in North Africa/Middle East to 77.4/100 000 cases/y in Sub-Saharan Africa and South Asia. The estimated total number of typhoid fever episodes in 2010 was 13.5 million (interquartile range 9.1–17.8 million). The adjusted estimate accounting for the low sensitivity of blood cultures for isolation of the bacteria was 26.9 million (interquartile range 18.3–35.7 million) episodes. These findings are comparable to the most recent analysis of global typhoid fever morbidity, which reported crude and adjusted estimates of 10.8 million and 21.7 million typhoid fever episodes globally in 2000. Conclusion Typhoid fever remains a significant health burden, especially in low- and middle-income countries. Despite the availability of more recent data on both enteric fevers, additional research is needed in many regions, particularly Africa, Latin America and other developing countries.
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              Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid.

              Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                17 July 2015
                July 2015
                : 9
                : 7
                : e0003859
                Affiliations
                [1 ]State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
                [2 ]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China
                [3 ]Center for Disease Control and Prevention of Yuanjiang County, Yunnan, China
                [4 ]Center for Disease Control and Prevention of Yuxi City, Yunnan, China
                [5 ]International Emerging Infections Program, US Centers for Disease Control and Prevention, Beijing, China
                [6 ]Global Disease Detection Branch, Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                Massachusetts General Hospital, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BK MY BY ZW SWa. Performed the experiments: MY BY XZ YZ BD RY. Analyzed the data: BK MY BY SWu JDK BP. Wrote the paper: BK MY SWu JDK.

                Article
                PNTD-D-14-02058
                10.1371/journal.pntd.0003859
                4506061
                26186586
                25eb2f18-d50e-414b-b5bb-6d1a2dcbb38d

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                History
                : 25 November 2014
                : 29 May 2015
                Page count
                Figures: 4, Tables: 1, Pages: 14
                Funding
                This work was supported by the Priority Project on Infectious Disease Control and Prevention [BK grant numbers 2012ZX10004215, 2008ZX10004-008] from the Ministry of Science and Technology of the People's Republic of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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