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Publication Serological evidence and risk factors for swine influenza infections among Chinese swine workers in guangdong province(Public Library of Science, 2015) Ma M.; Anderson B.D.; Wang T.; Chen Y.; Zhang D.; Gray G.C.; Lu J.; DUKE-NUS MEDICAL SCHOOLDuring July to September 2014, we performed a controlled, cross-sectional, seroepidemiologic study among 203 swine workers and 115 control subjects in Guangdong Province. Sera were tested using a hemagglutination inhibition assay against locally-isolated swine H3N2 and H1N1 viruses and commercially-obtained human influenza viral antigens. We found swine workers had a greater prevalence and odds of seropositivity against the swine H3N2 virus (17.3% vs. 7.0%; adjusted OR, 3.4; 95% CI, 1.1 -10.7). Younger age, self-report of a respiratory illness during the last 12 months, and seropositivity against seasonal H3N2 virus were identified as significant risk factors for seropositivity against swine H3N2 virus. As swine workers in China may be exposed to novel influenza viruses, it seems prudent for China to conduct special surveillance for such viruses among them. It also seems wise to offer such workers seasonal influenza vaccines with a goal to reduce cross-species influenza virus transmission. © 2015 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Publication Epidemiologic Features and Environmental Risk Factors of Severe Fever with Thrombocytopenia Syndrome, Xinyang, China(Public Library of Science, 2014) Liu K.; Cui N.; Fang L.-Q.; Wang B.-J.; Lu Q.-B.; Peng W.; Li H.; Wang L.-Y.; Liang S.; Wang H.-Y.; Zhang Y.-Y.; Zhuang L.; Yang H.; Gray G.C.; de Vlas S.J.; Liu W.; Cao W.-C.; DUKE-NUS MEDICAL SCHOOLBackground:Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in rural areas of Central China in 2009, caused by a novel bunyavirus, SFTS virus (SFTSV). The disease usually presents as fever, thrombocytopenia, and leukocytopenia, with case-fatality rates ranging from 2.5% to 30%. Haemaphysalis longicornis was suspected to be the most likely vector of SFTSV. By the end of 2012, the disease had expanded to 13 provinces of China. SFTS patients have been reported in Japan and South Korea, and a disease similar to SFTS has been reported in the United States.Methodology/Principal Findings:We characterized the epidemiologic features of 504 confirmed SFTS cases in Xinyang Region, the most severely SFTS-afflicted region in China from 2011 to 2012, and assessed the environmental risk factors. All cases occurred during March to November, with the epidemic peaking from May to July. The patients' ages ranged from 7 to 87 years (median 61 years), and the annual incidence increased with age (? 2 test for trend, P<0.001). The female-to-male ratio of cases was 1.58, and 97.0% of the cases were farmers who resided in the southern and western parts of the region. The Poisson regression analysis revealed that the spatial variations of SFTS incidence were significantly associated with the shrub, forest, and rain-fed cropland areas.Conclusions:The distribution of SFTS showed highly significant temporal and spatial heterogeneity in Xinyang Region, with the majority of SFTS cases being elderly farmers who resided in the southern and western parts of the region, mostly acquiring infection between May and July when H. longicornis is highly active. The shrub, rain-fed, and rain-fed cropland areas were associated with high risk for this disease. © 2014 Liu et al.Publication Prospective Study of Avian Influenza Virus Infections among Rural Thai Villagers(Public Library of Science, 2013) Krueger W.S.; Khuntirat B.; Yoon I.-K.; Blair P.J.; Chittagarnpitch M.; Putnam S.D.; Supawat K.; Gibbons R.V.; Bhuddari D.; Pattamadilok S.; Sawanpanyalert P.; Heil G.L.; Gray G.C.; DUKE-NUS MEDICAL SCHOOLBackground:In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses.Methods:After enrollment, participants were contacted weekly for 24mos for acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses.Results:Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2) virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80). While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2) at the 24-month encounter. One subject had an elevated titer (1:20) against H5N1 during follow-up.Conclusions:From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in humans.Publication Sparse evidence of MERS-CoV infection among animal workers living in Southern Saudi Arabia during 2012(2015) Memish, Z.A; Alsahly, A; Masri, M.al; Heil, G.L; Anderson, B.D; Peiris, M; Khan, S.U; Gray, G.C; DUKE-NUS MEDICAL SCHOOLMiddle East respiratory syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that primarily causes respiratory illness. We conducted a seroprevalence study of banked human serum samples collected in 2012 from Southern Saudi Arabia. Sera from 300 animal workers (17% with daily camel exposure) and 50 non-animal-exposed controls were examined for serological evidence of MERS-CoV infection by a pseudoparticle MERS-CoV spike protein neutralization assay. None of the sera reproducibly neutralized the MERS-CoV-pseudotyped lentiviral vector. These data suggest that serological evidence of zoonotic transmission of MERS-CoV was not common among animal workers in Southern Saudi Arabia during July 2012. © 2014 The Authors.Publication Little evidence of avian or equine influenza virus infection among a cohort of Mongolian adults with animal exposures, 2010-2011(Public Library of Science, 2014) Khurelbaatar N.; Krueger W.S.; Heil G.L.; Darmaa B.; Ulziimaa D.; Tserennorov D.; Baterdene A.; Anderson B.D.; Gray G.C.; DUKE-NUS MEDICAL SCHOOLAvian (AIV) and equine influenza virus (EIV) have been repeatedly shown to circulate among Mongolia's migrating birds or domestic horses. In 2009, 439 Mongolian adults, many with occupational exposure to animals, were enrolled in a prospective cohort study of zoonotic influenza transmission. Sera were drawn upon enrollment and again at 12 and 24 months. Participants were contacted monthly for 24 months and queried regarding episodes of acute influenza-like illnesses (ILI). Cohort members confirmed to have acute influenza A infections, permitted respiratory swab collections which were studied with rRT-PCR for influenza A. Serologic assays were performed against equine, avian, and human influenza viruses. Over the 2 yrs of follow-up, 100 ILI investigations in the cohort were conducted. Thirty-six ILI cases (36%) were identified as influenza A infections by rRT-PCR; none yielded evidence for AIV or EIV. Serological examination of 12 mo and 24 mo annual sera revealed 37 participants had detectable antibody titers (?1:10) against studied viruses during the course of study follow-up: 21 against A/Equine/Mongolia/01/2008(H3N8); 4 against an avian A/Teal/Hong Kong/w3129(H6N1), 11 against an avian-like A/Hong Kong/1073/1999(H9N2), and 1 against an avian A/Migrating duck/Hong Kong/MPD268/2007(H10N4) virus. However, all such titers were <1:80 and none were statistically associated with avian or horse exposures. A number of subjects had evidence of seroconversion to zoonotic viruses, but the 4-fold titer changes were again not associated with avian or horse exposures. As elevated antibodies against seasonal influenza viruses were high during the study period, it seems likely that cross-reacting antibodies against seasonal human influenza viruses were a cause of the low-level seroreactivity against AIV or EIV. Despite the presence of AIV and EIV circulating among wild birds and horses in Mongolia, there was little evidence of AIV or EIV infection in this prospective study of Mongolians with animal exposures. © 2014 Khurelbaatar et al.Publication A review of evidence that equine influenza viruses are zoonotic(2016) Xie, T; Anderson, B.D; Daramragchaa, U; Chuluunbaatar, M; Gray, G.C; DUKE-NUS MEDICAL SCHOOLAmong scientists, there exist mixed opinions whether equine influenza viruses infect man. In this report, we summarize a 2016 systematic and comprehensive review of the English, Chinese, and Mongolian scientific literature regarding evidence for equine influenza virus infections in man. Searches of PubMed, Web of Knowledge, ProQuest, CNKI, Chongqing VIP Database, Wanfang Data and MongolMed yielded 2831 articles, of which 16 met the inclusion criteria for this review. Considering these 16 publications, there was considerable experimental and observational evidence that at least H3N8 equine influenza viruses have occasionally infected man. In this review we summarize the most salient scientific reports. © 2016 by the authors; licensee MDPI, Basel, Switzerland.Publication Occupational exposure to Streptococcus suis among US swine workers(2008) Smith, T.C; Capuano, A.W; Boese, B; Myers, K.P; Gray, G.C; DUKE-NUS MEDICAL SCHOOLDespite numerous cases of human infection with Streptococcus suis worldwide, human disease is rarely diagnosed in North America. We studied 73 swine-exposed and 67 non-swine-exposed US adults for antibodies to S. suis serotype 2. Serologic data suggest that human infection with S. suis occurs more frequently than currently documented.Publication Surveillance for respiratory syncytial virus and parainfluenza virus among patients hospitalized with pneumonia in Sarawak, Malaysia(2018) Fieldhouse J.K.; Toh T.-H.; Lim W.-H.; Ting J.; Ha S.-J.; Hii K.-C.; Kong C.-I.; Wong T.-M.; Wong S.-C.; Warkentien T.E.; Gray G.C.; DUKE-NUS MEDICAL SCHOOLBackground: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are frequent causes of pneumonia and death among children at Sibu and Kapit Hospitals in Sarawak, Malaysia. Objectives To determine the prevalence and risk factors for RSV subtypes A and B and PIV types 1±4 among patients hospitalized with pneumonia. Methods: In a cross-sectional, pilot study nasopharyngeal swabs were studied with real-time reverse transcription polymerase chain reaction assays. Concurrently, we helped Sibu and Kapit Hospitals adapt their first molecular diagnostics for RSV and PIV. Results: Of 129 specimens collected (June to July 2017), 39 tested positive for RSV-A (30.2%), two were positive for RSV B (1.6%), one was positive for PIV-3 (0.8%) and one was positive for PIV-4 (0.8%). No samples were positive for PIV-1 or PIV-2. Of the 39 RSV-A positive specimens, 46.2% were collected from children under one year of age and only 5.1% were from patients over the age of 18. A multivariable analysis found the odds of children <1 year of age testing positive for RSV-A were 32.7 (95% CI: 3.9, 276.2) times larger than >18 years of age, and the odds of patients hospitalized at Kapit Hospital testing positive for RSV-A were 3.2 (95% CI: 1.3, 7.8) times larger than patients hospitalized at Sibu Hospital. Conclusion: This study found an unusually high prevalence of RSV-A among pneumonia patients admitted to the two hospitals. Subsequently, Sibu Hospital adapted the molecular assays with the goal of providing more directed care for such pneumonia patients. © 2018 Public Library of Science. All rights reserved.Publication Training initiatives within the AFHSC-Global Emerging Infections Surveillance and Response System: Support for IHR (2005)(2011) Otto, J.L; Baliga, P; Sanchez, J.L; Johns, M.C; Gray, G.C; Grieco, J; Lescano, A.G; Mothershead, J.L; Wagar, E.J; Blazes, D.L; DUKE-NUS MEDICAL SCHOOLTraining is a key component of building capacity for public health surveillance and response, but has often been difficult to quantify. During fiscal 2009, the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) supported 18 partner organizations in conducting 123 training initiatives in 40 countries for 3,130 U.S. military, civilian and host-country personnel. The training assisted with supporting compliance with International Health Regulations, IHR (2005). Training activities in pandemic preparedness, outbreak investigation and response, emerging infectious disease (EID) surveillance and pathogen diagnostic techniques were expanded significantly. By engaging local health and other government officials and civilian institutions, the U.S. militarys role as a key stakeholder in global public health has been strengthened and has contributed to EID-related surveillance, research and capacity-building initiatives specified elsewhere in this issue. Public health and emerging infections surveillance training accomplished by AFHSC-GEIS and its Department of Defense (DoD) partners during fiscal 2009 will be tabulated and described. © 2011 Otto et al; licensee BioMed Central Ltd.Publication Risk Distribution of Human Infections with Avian Influenza H7N9 and H5N1 virus in China(Nature Publishing Group, 2015) Li, X.-L; Yang, Y; Sun, Y; Chen, W.-J; Sun, R.-X; Liu, K; Ma, M.-J; Liang, S; Yao, H.-W; Gray, G.C; Fang, L.-Q; Cao, W.-C; DUKE-NUS MEDICAL SCHOOLIt has been documented that the epidemiological characteristics of human infections with H7N9 differ significantly between H5N1. However, potential factors that may explain the different spatial distributions remain unexplored. We use boosted regression tree (BRT) models to explore the association of agro-ecological, environmental and meteorological variables with the occurrence of human cases of H7N9 and H5N1, and map the probabilities of occurrence of human cases. Live poultry markets, density of human, coverage of built-up land, relative humidity and precipitation were significant predictors for both. In addition, density of poultry, coverage of shrub and temperature played important roles for human H7N9 infection, whereas human H5N1 infection was associated with coverage of forest and water body. Based on the risks and distribution of ecological characteristics which may facilitate the circulation of the two viruses, we found Yangtze River Delta and Pearl River Delta, along with a few spots on the southeast coastline, to be the high risk areas for H7N9 and H5N1. Additional, H5N1 risk spots were identified in eastern Sichuan and southern Yunnan Provinces. Surveillance of the two viruses needs to be enhanced in these high risk areas to reduce the risk of future epidemics of avian influenza in China.