Chinese Center For Disease Control and Prevention

This Viewpoint summarizes key epidemiologic and clinical findings from all cases of coronavirus disease 2019 (COVID-19) reported through February 11, 2020, in mainland China, and case trends in response to government attempts to control and contain the infection.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

IMPORTANCE: Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW: Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS: In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globally was prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancer was the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancer was breast cancer (2.4 million cases). Breast cancer was also the leading cause of cancer deaths and DALYs for women (523 000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1% [95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE: As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.

This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.

BACKGROUND: Public health is a priority for the Chinese Government. Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance. This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level. METHODS: We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017. We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk. We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI). FINDINGS: Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017. Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017. Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017. Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs. All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88. The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain. The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4). INTERPRETATION: China has made substantial progress in reducing the burden of many diseases and disabilities. Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system. FUNDING: China National Key Research and Development Program and Bill & Melinda Gates Foundation.

Pesticides are indispensable in agricultural production. They have been used by farmers to control weeds and insects, and their remarkable increases in agricultural products have been reported. The increase in the world's population in the 20th century could not have been possible without a parallel increase in food production. About one-third of agricultural products are produced depending on the application of pesticides. Without the use of pesticides, there would be a 78% loss of fruit production, a 54% loss of vegetable production, and a 32% loss of cereal production. Therefore, pesticides play a critical role in reducing diseases and increasing crop yields worldwide. Thus, it is essential to discuss the agricultural development process; the historical perspective, types and specific uses of pesticides; and pesticide behavior, its contamination, and adverse effects on the natural environment. The review study indicates that agricultural development has a long history in many places around the world. The history of pesticide use can be divided into three periods of time. Pesticides are classified by different classification terms such as chemical classes, functional groups, modes of action, and toxicity. Pesticides are used to kill pests and control weeds using chemical ingredients; hence, they can also be toxic to other organisms, including birds, fish, beneficial insects, and non-target plants, as well as air, water, soil, and crops. Moreover, pesticide contamination moves away from the target plants, resulting in environmental pollution. Such chemical residues impact human health through environmental and food contamination. In addition, climate change-related factors also impact on pesticide application and result in increased pesticide usage and pesticide pollution. Therefore, this review will provide the scientific information necessary for pesticide application and management in the future.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

BACKGROUND: Infection of poultry with influenza A subtype H7 viruses occurs worldwide, but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013, three urban residents of Shanghai or Anhui, China, presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus. METHODS: We obtained and analyzed clinical, epidemiologic, and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase-polymerase-chain-reaction assays, viral culturing, and sequence analyses. RESULTS: A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin, with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever, cough, and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died. CONCLUSIONS: Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

BACKGROUND: Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing. METHODS: We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples. RESULTS: We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness. CONCLUSIONS: A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).

Abstract Background Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29 th , 2020. Results The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P <0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

BACKGROUND: The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. METHODS: Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. RESULTS: In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. CONCLUSIONS: Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Neutralizing antibodies could potentially be used as antivirals against the coronavirus disease 2019 (COVID-19) pandemic. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. The antibodies B38 and H4 block binding between the spike glycoprotein receptor binding domain (RBD) of the virus and the cellular receptor angiotensin-converting enzyme 2 (ACE2). A competition assay indicated different epitopes on the RBD for these two antibodies, making them a potentially promising virus-targeting monoclonal antibody pair for avoiding immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.

BACKGROUND: Large blood-based prospective studies can provide reliable assessment of the complex interplay of lifestyle, environmental and genetic factors as determinants of chronic disease. METHODS: The baseline survey of the China Kadoorie Biobank took place during 2004-08 in 10 geographically defined regions, with collection of questionnaire data, physical measurements and blood samples. Subsequently, a re-survey of 25,000 randomly selected participants was done (80% responded) using the same methods as in the baseline. All participants are being followed for cause-specific mortality and morbidity, and for any hospital admission through linkages with registries and health insurance (HI) databases. RESULTS: Overall, 512,891 adults aged 30-79 years were recruited, including 41% men, 56% from rural areas and mean age was 52 years. The prevalence of ever-regular smoking was 74% in men and 3% in women. The mean blood pressure was 132/79 mmHg in men and 130/77 mmHg in women. The mean body mass index (BMI) was 23.4 kg/m(2) in men and 23.8 kg/m(2) in women, with only 4% being obese (>30 kg/m(2)), and 3.2% being diabetic. Blood collection was successful in 99.98% and the mean delay from sample collection to processing was 10.6 h. For each of the main baseline variables, there is good reproducibility but large heterogeneity by age, sex and study area. By 1 January 2011, over 10,000 deaths had been recorded, with 91% of surviving participants already linked to HI databases. CONCLUSION: This established large biobank will be a rich and powerful resource for investigating genetic and non-genetic causes of many common chronic diseases in the Chinese population.

This study began with the desire of the University of North Carolina (UNC), Chapel Hill (CH) Principal Investigator (PI) to be able to examine across space and time the ways economic and social change affected a range of health behaviours in a large country. China was selected because of its unique opening up of its economic and social system. In 1986 no longitudinal surveys existed in China and all surveys were either very narrow health, economic or demographic surveys. Furthermore, no raw data from any survey had been allowed out of the country. Since China's reform and open policy, the country was being transformed from one facing famine and extreme food shortages to one where the food supply addressed basic needs and the initial states of a major transformation of the food distribution and marketing system was occurring. With this as background, two UNC faculty members, Barry Popkin and Gail Henderson, a China scholar, began the process in 1986 of meeting a range of University and government officials to discuss this work. The Chinese Center for Disease Control and Prevention (CCDC) (formerly the Chinese Academy of Preventive Medicine, CAPM) was selected. The CCDC, under the leadership of Madame Chunming Chen, was very enthusiastic about the challenges of such an approach to understanding the interplay of socio-economic change and health and decided to invest the academy's own funds to collaborate on this initiative. An agreement that focused on publication, data ownership and data dissemination of the results was established. No funding agencies thought such an initiative could be undertaken and the data base obtained by the US institution for use and dissemination. As a result, a small grant of $60 000 from the Carolina Population Center (CPC) was the only available funding to initiate the first survey. The China Health and Nutrition Survey (CHNS) was established. The goal was to develop a multipurpose longitudinal survey that would allow the group to examine a series of economic, sociological, demographic and health questions of interest to the CAPM and these scholars. Professor John Akin joined Popkin and Henderson in work on the initial effort. Once the group proved able to collect the data and to get the raw data files out of China, a program project application was submitted to National Institute of Child Health and Human Development (NICHD) that included two additional waves of CHNS data collection. This was funded and all subsequent survey waves were funded by NICHD-funded R01s. Only later did the Chinese Ministry of Health decide the surveys were important, and the ministry instructed the collaborating provinces to place priority on long-term collaboration. The active involvement of the Minister of Health and others in the ministry has provided important political protection for the CHNS and also has provided continued counterpart partial financial support. Chinese colleagues are full and active partners in the CHNS project and have primary responsibility for data collection. Over the life of the project they have spent considerable time in CH working with the UNC–CH group on data analysis and training activities, and they plan to continue these efforts. Professors Keyou Ge, then Fengying Zhai, and now Bing Zhang lead the project for the CCDC. Professor Shuigao Jin, a statistician and computer expert, initially headed the component dealing with sampling and database development. Professor Huijun Wang is a key member of field work, data cleaning and data analysis. At one time Professor Shufa Du headed the project in China and now, as a faculty member at UNC, plays a major role in working with the CHNS. Part of the reason for the careful selection of the collaborator for the CHNS was the desire to insulate this study from the political and institutional problems that have hampered many subsequent survey research projects conducted jointly by US and Chinese institutions. By partnering as we have, we have been successful in continuing this survey during periods in China when many other western-funded social science-related surveys were discontinued. In 2009 the Department of Laboratory Medicine of China-Japan Friendship Hospital (CJFH), Ministry of Health (MOH) joined this project as the lead agency for the collection, storage and analysis of biospecimens. Dr Shengkai Yan leads the work related to biospecimens. This survey was designed to cover key public health risk factors and health outcomes, demographic, social and economic factors in depth at the individual, household and community levels. This in-depth survey collects data on occupations; incomes and benefits of working-age household members; time use; diet and nutritional status; activities of daily living, health status and use of health services; marriages, birth preference and pregnancies of reproductive-age women; mass media and body images; household size and composition; living arrangements; care of children and elders; housing conditions; land ownership; and limited household asset ownership. Individual health-related data are highly detailed, and include carefully measured dietary intake, physical activity, smoking and drinking data, anthropometrics, blood pressure and limited clinical data from all respondents. Beginning with the CHNS 2009, spatial coordinates on all respondents and key community resources, fasting blood for all respondents ≥7 years old, and toenail samples for all respondents ≥2 years old are being collected. It also collects detailed community economic, social, demographic and infrastructural data. The CHNS sample was not designed to be representative of China but to be randomly selected and to capture a range of economic and demographic circumstances and to provide data from randomly selected households in eight provinces—Liaoning, Shandong, Henan, Jiangsu, Hubei, Hunan, Guizhou and Guangxi (from north to south). Data to create a representative provincial level sample could not be obtained in 1988. A multistage, random cluster process was used to draw the sample in each of the provinces. Counties and cities in each province were stratified by income (low, middle and high) and a weighted sampling scheme was used to randomly select four counties and two cities in each province. Villages and townships within the counties and urban and suburban neighbourhoods within the cities were selected randomly. In each community, 20 households were randomly selected and all household members were interviewed; only preschoolers and young adults aged 20–45 years were surveyed in 1989 due to constraints of funding. The current sample consists of 216 communities from nine provinces (Heilongjiang province was enrolled as a ninth province in 1997), comprising of 36 urban neighbourhoods, 36 suburban neighbourhoods, 36 towns and 108 villages. The household sample was 4020 in 1989 and 4467 in 2006. For individuals, it was 15927 in 1989 and 18 764 in 2006. The CHNS rounds have been completed in 1989, 1991, 1993, 1997, 2000, 2004, 2006 and now 2009. The CHNS 2011 is also funded and will be undertaken. We will then propose two new rounds to the National Institutes of Health (NIH) with a request for a second round of fasting blood and toenail samples. Due to cancellation of travel linked with the SARS outbreak, the CHNS 2003 was shifted to 2004. All funding has come from the National Institute of Child Health and Development with one small National Science Foundation, an institutional development and training grant from the NIH Fogarty Institute, CPC support for the first wave, and some small foundation support. The CCDC and provincial CDCs have provided strong cofunding support for local field survey costs, including car, manpower and per diems in the initial four to five surveys. Essentially all rounds of the CHNS have collected identical data from the community and household. The CHNS 1989, undertaken as the first survey to collect individual dietary intake data in China, obtained these dietary, clinical and anthropometric data from children aged <6 years and all adults aged 20–45 years. All subsequent surveys have obtained clinical, dietary, anthropometric and all other individual data from each household member (Table 1). Key domains of data—CHNS HH: Household; IADL: Instrumental activities of daily living; ADL: Activities of Daily Living; GPS: Global positioning system. Key domains of data—CHNS HH: Household; IADL: Instrumental activities of daily living; ADL: Activities of Daily Living; GPS: Global positioning system. Response rates and attrition are very complex to determine with this survey, because the participants who left in one survey year may have moved back in a later year, and because, since 1997, we have recruited new participants as replenishment samples if a community has less than 20 households or if participants have formed a new household or separated from their family into a new housing unit in the same community (Tables 2 and 3). In 1997, one province was unable to participate in the survey for natural disaster, political and administrative reasons, namely the Liaoning Province, which could not take on Beijing-initiated projects. We added a new province, Heilongjiang, in CHNS 1997 and then surveyed both the old returning province and the new one in CHNS 2000 and all subsequent surveys. If we define response rate based on those who participated in previous survey rounds remaining in the current survey, our response rates were ∼88% at individual level and 90% at household level. If we define response rate based on those who participated in 1989 and remained in the last round in 2006, they were 63 and 69%, respectively. CHNS response rates at the individual and household levels aBased on previous year. bBased on 1989 samples. CHNS response rates at the individual and household levels aBased on previous year. bBased on 1989 samples. CHNS survey participation rate for 1989 households and individuals CHNS survey participation rate for 1989 households and individuals We have had several major causes of loss to follow-up. The first is missing people, whom we could not find, due to travel, hours of work or play, and/or refusal to come for anthropometric and clinical exams. The second is school children who were in boarding schools, a practice that greatly accelerated in 2004 and 2006, and who entered colleges and universities. The third is migrant work for those aged ≥16 years. And last, natural disasters and major redevelopment of housing in all large urban centres added to these relocations. For example, 1997 was the year our provinces experienced a major natural crisis. Flooding affected ∼25% of our rural sample. The villages were flooded for 3 months and villagers moved away in scattered fashion, but most individuals returned later. In CHNS 2006, we found 13 households in one community of Hunan province and many more in other provinces that had returned the previous year. A new province—Heilongjiang—was added and Liaoning Province rejoined in 2000; therefore, the total sample size increased to approximately 19 000 individuals who lived in 4500 households. Table 3 shows that >75% of households participated in five to seven surveys and an additional 17% in three to four surveys. We defined individual participation very conservatively as those who provided 3 days of individual dietary data, employment, occupational and income data (if an adult). First, as noted, 7.25% of the sample has died; 66% have been in four or more rounds of the survey (Table 3). These levels of individual response will be increased significantly with the survey of missed individuals during the Chinese New Year proposed for the new rounds. Details on the survey in general are on the CHNS web site: http://www.cpc.unc.edu/projects/china. Our lost-to-follow-up rate increased in the past two waves. To remedy these problems, our team, along with provincial collaborators, spent >18 months discussing options. We have piloted new strategies that will be instituted in 2009 and refined for 2011. The first change is to have interviewers return to the communities during the Spring Festival to attempt to locate families and individuals we previously missed. The second change is to go to the boarding schools of all children during the week and obtain their dietary, anthropometric and other relevant data that parents will not be able to report (e.g. television viewing, physical activity). This second change seems to work and will be used as one option for both urban and rural areas to attempt to increase the age 4–17 population response rate to 90%. We did some research in two provinces around the Spring Festival re-interview but could not get an adequate sample from which to prepare exact statistics. We expect to see a large increase because many migrant farmers who work in other areas will return to their home during the Spring Festival. In four provinces we also tested undertaking the survey in all township boarding schools and this captured most of the children missing from the household surveys for CHNS 2006. Both of these changes will be implemented for all provinces in the CHNS 2009. Table 4 shows the percentages of the study participants who have died. Because the number of deaths is substantial, analyses have been published with these individuals as a focus. Percent of 1989 participants who died between the prior survey and 2006 Percent of 1989 participants who died between the prior survey and 2006 The CHNS has been used for an array of research across dozens of disciplines and journals. The impact can be measured by the publications of the individuals and institutions that have downloaded the data. Among important policy results have been research used to launch a national fortification law for fortifying soy sauce and flour with iron and other micronutrients, the basis for World Bank poverty reduction programs in a number of poor counties, a large series of studies to justify national programs linking agricultural price policy with nutrition to attempt to increase soybean consumption and other price research being used to consider some ways to reduce caloric intake and weight gain, and the basis for many national and provincial programs addressing poor dietary and activity patterns and increased obesity.1–3 The obesity work has shown how shifting from bikes and walking to cars and motorcycles has increased incident obesity, and how declines in home production and shifts toward more reduced-activity market-related occupations have increased the risk of obesity.4,5 Other work in nutrition and chronic disease has shown the body mass index–hypertension relationships in Chinese people are much steeper than in the USA among Blacks and Whites,6 and the shifting dietary and activity patterns among the poor that have heralded an increased burden of obesity among the poor.7 The major strength of the CHNS is the ability to capture enormous heterogeneity and change spatially and temporally in one of the most rapidly changing environments in the world. Because of its long duration and wide geographic coverage, the CHNS can document the dramatic economic, social, behavioural and health status changes that have characterized China in the past several decades. Key weaknesses include the loss-to-follow-up data, particularly among individuals. This came partially because of the PI's cautiousness in obtaining adequate NIH funding. A second major weakness is the lack of sampling weights, an issue that we wish we had tried to address in 1987 through more efforts to work with the State Statistical Bureau and involvement of a more experienced Chinese sampling researcher. In addition, we would have liked to collect GPS data earlier, but the Chinese government did not allow this until 2009 and we would have liked to have foreseen more of the major food system changes and obtained contextual data to capture the early stages of these changes (mainly the shift toward modern large supermarket food systems and more data on media exposure). All data are available free to scholars at the web site http://www.cpc.unc.edu/projects/china/data/data.html. We have created 51 new datasets, known as CHNS Longitudinal Master Files, available for download in SAS transport format, including those shown in Table 5. These new master files are designed to make longitudinal analysis of the CHNS Survey data much easier. All variable names are standardized across all survey years when they represent the same survey question. With a few exceptions, they are standardized to the 3700 variable names. Data formatting is standardized across all survey years. Master longitudinal CHNS files Master longitudinal CHNS files The exceptions are requests for information that can provide ways to locate the sample. The contextual data require some confidentiality forms be completed prior to release. The Food Composition Table data are not available as they are controlled by separate Chinese authorities. GPS coordinates will not be provided; however, procedures to pay for linkages and for collection of additional coordinates will be provided on the website. Also, by the middle or end of 2011, provisions for obtaining access to buffy coat, biomarker and other data will be available. All biomarker data are stored at the CJFH. National Institutes of Health (RO1-HD30880, DK056350 and RO1-HD38700) and the Fogarty International Center. The authors thank the National Institute of Nutrition and Food Safety, China Center for Disease Control, the National Institutes of Health (NIH) (R01-HD30880, DK056350 and R01-HD38700) and the Fogarty International Center, NIH, for financial support for the CHNS data collection and analysis files from 1989 to 2006 and both parties plus the China-Japan Friendship Hospital, Ministry of Health for support for CHNS 2009 and future surveys. They also wish to thank Ms Frances L. Dancy for administrative assistance; Mr James Terry and Dr Phil Bardsley for managing the CHNS file development; our numerous colleagues at UNC and across the USA who have assisted us; and our hundreds of staff in China for undertaking repeatedly this very complex survey. None of the authors has conflict of interests of any type with respect to this manuscript. Conflict of interest: None declared.

In March 2012, the SAGE Working Group on Vaccine Hesitancy was convened to define the term "vaccine hesitancy", as well as to map the determinants of vaccine hesitancy and develop tools to measure and address the nature and scale of hesitancy in settings where it is becoming more evident. The definition of vaccine hesitancy and a matrix of determinants guided the development of a survey tool to assess the nature and scale of hesitancy issues. Additionally, vaccine hesitancy questions were piloted in the annual WHO-UNICEF joint reporting form, completed by National Immunization Managers globally. The objective of characterizing the nature and scale of vaccine hesitancy issues is to better inform the development of appropriate strategies and policies to address the concerns expressed, and to sustain confidence in vaccination. The Working Group developed a matrix of the determinants of vaccine hesitancy informed by a systematic review of peer reviewed and grey literature, and by the expertise of the working group. The matrix mapped the key factors influencing the decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine-specific. These categories framed the menu of survey questions presented in this paper to help diagnose and address vaccine hesitancy.

International audience

The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.

BACKGROUND: Foodborne diseases are globally important, resulting in considerable morbidity and mortality. Parasitic diseases often result in high burdens of disease in low and middle income countries and are frequently transmitted to humans via contaminated food. This study presents the first estimates of the global and regional human disease burden of 10 helminth diseases and toxoplasmosis that may be attributed to contaminated food. METHODS AND FINDINGS: Data were abstracted from 16 systematic reviews or similar studies published between 2010 and 2015; from 5 disease data bases accessed in 2015; and from 79 reports, 73 of which have been published since 2000, 4 published between 1995 and 2000 and 2 published in 1986 and 1981. These included reports from national surveillance systems, journal articles, and national estimates of foodborne diseases. These data were used to estimate the number of infections, sequelae, deaths, and Disability Adjusted Life Years (DALYs), by age and region for 2010. These parasitic diseases, resulted in 48.4 million cases (95% Uncertainty intervals [UI] of 43.4-79.0 million) and 59,724 (95% UI 48,017-83,616) deaths annually resulting in 8.78 million (95% UI 7.62-12.51 million) DALYs. We estimated that 48% (95% UI 38%-56%) of cases of these parasitic diseases were foodborne, resulting in 76% (95% UI 65%-81%) of the DALYs attributable to these diseases. Overall, foodborne parasitic disease, excluding enteric protozoa, caused an estimated 23.2 million (95% UI 18.2-38.1 million) cases and 45,927 (95% UI 34,763-59,933) deaths annually resulting in an estimated 6.64 million (95% UI 5.61-8.41 million) DALYs. Foodborne Ascaris infection (12.3 million cases, 95% UI 8.29-22.0 million) and foodborne toxoplasmosis (10.3 million cases, 95% UI 7.40-14.9 million) were the most common foodborne parasitic diseases. Human cysticercosis with 2.78 million DALYs (95% UI 2.14-3.61 million), foodborne trematodosis with 2.02 million DALYs (95% UI 1.65-2.48 million) and foodborne toxoplasmosis with 825,000 DALYs (95% UI 561,000-1.26 million) resulted in the highest burdens in terms of DALYs, mainly due to years lived with disability. Foodborne enteric protozoa, reported elsewhere, resulted in an additional 67.2 million illnesses or 492,000 DALYs. Major limitations of our study include often substantial data gaps that had to be filled by imputation and suffer from the uncertainties that surround such models. Due to resource limitations it was also not possible to consider all potentially foodborne parasites (for example Trypanosoma cruzi). CONCLUSIONS: Parasites are frequently transmitted to humans through contaminated food. These estimates represent an important step forward in understanding the impact of foodborne diseases globally and regionally. The disease burden due to most foodborne parasites is highly focal and results in significant morbidity and mortality among vulnerable populations.

Abstract Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3–6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

BACKGROUND: Since the start of the 2009 influenza A pandemic (H1N1pdm), the World Health Organization and its member states have gathered information to characterize the clinical severity of H1N1pdm infection and to assist policy makers to determine risk groups for targeted control measures. METHODS AND FINDINGS: Data were collected on approximately 70,000 laboratory-confirmed hospitalized H1N1pdm patients, 9,700 patients admitted to intensive care units (ICUs), and 2,500 deaths reported between 1 April 2009 and 1 January 2010 from 19 countries or administrative regions--Argentina, Australia, Canada, Chile, China, France, Germany, Hong Kong SAR, Japan, Madagascar, Mexico, The Netherlands, New Zealand, Singapore, South Africa, Spain, Thailand, the United States, and the United Kingdom--to characterize and compare the distribution of risk factors among H1N1pdm patients at three levels of severity: hospitalizations, ICU admissions, and deaths. The median age of patients increased with severity of disease. The highest per capita risk of hospitalization was among patients <5 y and 5-14 y (relative risk [RR] = 3.3 and 3.2, respectively, compared to the general population), whereas the highest risk of death per capita was in the age groups 50-64 y and ≥65 y (RR = 1.5 and 1.6, respectively, compared to the general population). Similarly, the ratio of H1N1pdm deaths to hospitalizations increased with age and was the highest in the ≥65-y-old age group, indicating that while infection rates have been observed to be very low in the oldest age group, risk of death in those over the age of 64 y who became infected was higher than in younger groups. The proportion of H1N1pdm patients with one or more reported chronic conditions increased with severity (median = 31.1%, 52.3%, and 61.8% of hospitalized, ICU-admitted, and fatal H1N1pdm cases, respectively). With the exception of the risk factors asthma, pregnancy, and obesity, the proportion of patients with each risk factor increased with severity level. For all levels of severity, pregnant women in their third trimester consistently accounted for the majority of the total of pregnant women. Our findings suggest that morbid obesity might be a risk factor for ICU admission and fatal outcome (RR = 36.3). CONCLUSIONS: Our results demonstrate that risk factors for severe H1N1pdm infection are similar to those for seasonal influenza, with some notable differences, such as younger age groups and obesity, and reinforce the need to identify and protect groups at highest risk of severe outcomes. Please see later in the article for the Editors' Summary.