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Abstract Background Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. Methods The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. Results We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4–94.1%) and specificity of 90.0% (95% CI: 81.9–95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. Conclusion TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021

Abstract Background The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. Methods These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. Results Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. Conclusions This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide. Graphical Abstract

Abstract Lung adenocarcinoma (LUAD) is the most common and aggressive subtype of lung cancer, and coronavirus disease 2019 (COVID-19) has become a serious public health threat worldwide. Patients with LUAD and COVID-19 have a poor prognosis. Therefore, finding medications that can be used to treat COVID-19/LUAD patients is essential. Bioinformatics analysis was used to identify 20 possible metformin target genes for the treatment of COVID-19/LUAD. PTEN and mTOR may serve as hub target genes of metformin. Metformin may be able to cure COVID-19/LUAD comorbidity through energy metabolism, oxidoreductase NADH activity, FoxO signalling pathway, AMPK signalling system, and mTOR signalling pathway, among other pathways, according to the results of bioinformatic research. Metformin has ability to inhibit the proliferation of A549 cells, according to the results of colony formation and proliferation assays. In A549 cells, metformin increased glucose uptake and lactate generation, while decreasing ATP synthesis and the NAD+/NADH ratio. In summary, PTEN and mTOR may be potential targets of metformin for the treatment of COVID-19/LUAD. The mechanism by which metformin inhibits lung adenocarcinoma cell proliferation may be related to glucose metabolism regulated by PI3K/AKT signalling and mTOR signalling pathways. Our study provides a new theoretical basis for the treatment of COVID-19/LUAD.

Abstract Background Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. Methods A total of 3251 hrHPV-positive women aged 30–82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. Results CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 −) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). Conclusions PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. Trial registration ChiCTR2100048972. Registered on 19 July 2021.

Abstract Background More than half of the global population lives in areas at risk of dengue (DENV) transmission. Developing an efficient risk prediction system can help curb dengue outbreaks, but multiple variables, including mosquito-based surveillance indicators, still constrain our understanding. Mosquito or oviposition positive index (MOI) has been utilized in field surveillance to monitor the wild population density of Aedes albopictus in Guangzhou since 2005. Methods Based on the mosquito surveillance data using Mosq-ovitrap collection and human landing collection (HLC) launched at 12 sites in Guangzhou from 2015 to 2017, we established a MOI-based model of the basic dengue reproduction number (R 0) using the classical Ross-Macdonald framework combined with a linear mixed-effects model. Results During the survey period, the mean MOI and adult mosquito density index (ADI) using HLC for Ae. albopictus were 12.96 ± 17.78 and 16.79 ± 55.92, respectively. The R 0 estimated from the daily ADI (ADID) showed a significant seasonal variation. A 10-unit increase in MOI was associated with 1.08-fold (95% CI 1.05, 1.11) ADID and an increase of 0.14 (95% CI 0.05, 0.23) in the logarithmic transformation of R 0. MOI-based R 0 of dengue varied by month and average monthly temperature. During the active period of Ae. albopictus from April to November in Guangzhou region, a high risk of dengue outbreak was predicted by the MOI-based R 0 model, especially from August to October, with the predicted R 0 > 1. Meanwhile, from December to March, the estimates of MOI-based R 0 were < 1. Conclusions The present study enriched our knowledge about mosquito-based surveillance indicators and indicated that the MOI of Ae. albopictus could be valuable for application in estimating the R 0 of dengue using a statistical model. The MOI-based R 0 model prediction of the risk of dengue transmission varied by month and temperature in Guangzhou. Our findings lay a foundation for further development of a complex efficient dengue risk prediction system. Graphical Abstract

Abstract Background Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. Methods A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015–2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. Results A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. Conclusions Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management. Graphical Abstract

Abstract High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy.

Objective To study prevalence characteristics and change pattern of dominant virus strain of influenza epidemics in Guangzhou city and to provide evidence for formulating region-specific prevention and control measures. Methods Weekly influenza surveillance data of Guangzhou city, Guangdong province from 2015 to 2022 were collected from China Influenza Surveillance Information System. The positive rate series of influenza virus and its pathogen subtype were decomposed into trend/season/remainder component by using the seasonal-trend decomposition procedure based on locally weighted regression. By calculating covariance, the contribution rate of the obtained components to the fluctuation of positive rate was analyzed. Results Of 39 198 surveillance specimens sampled in the city during the 8-year period, 3 632 (9.27%) were positive for influenza virus nucleic acid. Trend series analysis showed that the positive rate fluctuated from 4.57% to 16.07%, with an increasing trend, during 2015 – 2019 and varied with a U-shape trajectory during 2020 – 2022. Winter-spring and spring-summer peaks of the positive rate were observed in season series analysis and the remainder component analysis revealed the highest fluctuation range of 48.96% for the positive rate in 2022. The positive rate of influenza A (H3N2) presented a similar season series to that of influenza B (Victoria), with winter and summer peaks, but the summer peaks of influenza A (H3N2) was later than that of influenza B (Victoria); the peak shape and prevalence duration (single peaks mainly in winter-spring season) of influenza A (H1N1) pdm09 positivity were similar to those of influenza B (Yamagata). In general, the remainder component was the main contributor to the fluctuation of the total positive rate, accounting for 59.16% of overall fluctuation (covariance of remainder component versus that of original series: 80.81/136.60), followed by season and trend component, accounting for 25.19% (34.41/136.60) and 15.68% (21.38/136.60) of overall fluctuation, respectively. Conclusion There were virus subtype-specific differences in seasonal peak and prevalence duration of influenza infection and random fluctuation exerted a greater effect than long-term trend and seasonal variation on influenza epidemic pattern in Guangzhou city.

Abstract Background The number of human rabies cases caused by pet dogs in Guangzhou has been decreasing after years of comprehensive interventions. Consequently, attacks by stray dogs become a major issue in rabies control. Objectives To share our experience of successfully dealing with rabies to provide some inspiration for prevention and control in countries and regions affected by it. Methods A multidisciplinary One Health response was initiated to control this outbreak. Rabies virus was detected by PCR in the brain tissue of the associated stray dog. The sequences were aligned with reference sequences downloaded from GenBank using ClustalX. The maximum likelihood method implemented in MEGA 5.0 software package was used in a phylogenetic analysis of the aligned sequences. Results Twelve patients with exposure to the stray dog were identified in the field investigation. Rabies vaccines and immunoglobulin were administered to all patients within 48 h. After 1 year of follow‐up, no exposed patients showed symptoms. Maximum likelihood analysis of the nucleotide sequences obtained from the PCR products indicated that the rabies virus in the dog was closely related to isolates from neighbouring provinces of Guangdong as well as those from surrounding countries of China. Conclusions Multidisciplinary One Health intervention is effective not only in the control of rabies but also in rapid emergency responses to attacks by rabid stray dogs.

Since the SARS-CoV-2 Omicron variant was first reported from South Africa, it has rapidly spread in over 100 countries. Only two cases infected by the Omicron variant were recently identified in China. The one case in Guangzhou has a relatively long incubation time and mild symptoms. Analysis of the complete viral genome sequence shows three missing Omicron unique mutations and one additional mutation in the newly characterized genome. These unique mutations may be related to the clinical presentation in this case.

Abstract Background Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance. Methods Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics. Results The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2–6%, 0.8–2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics. Conclusions The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically. Graphical Abstract

Background: Leptospirosis, which is an easily overlooked zoonotic disease, was once widespread in Guangzhou, China. However, due to the implementation of control measures, the number of cases is decreasing. Based on the characteristics of leptospirosis cases in Guangzhou, China, between 1955 and 2020, we describe the changes and achievements in prevention and control management strategies over that period. Methods: The development of the leptospirosis control system in Guangzhou occurred over three periods: Period I: 1955–1978; Period II: 1979–2000; and Period III: 2001–2020. Data about leptospirosis cases were obtained from the Guangzhou Center for Disease Control and Prevention (CDC) and national health departments. The demographic characteristics of leptospirosis patients were analyzed using descriptive statistics. Results: During Period I, only the Guangzhou CDC and medical institutions at every level participated in the leptospirosis control system. During Period II, additional types of organizations, including local CDCs, countryside committees, community committees, and the Patriotic Health Movement Commission, were involved in the control system. Additionally, strong links were established between different organizations. After entering Period III, an increasing number of departments joined the cooperation, and the management of human patients was expanded to include the management of host animals, and thus, the prevalence of leptospirosis was monitored and controlled in various ways. The leptospirosis control system in Guangzhou has been further improved. From 1955 to 2020, a total of 2501 leptospirosis cases were recorded in Guangzhou, and the number of cases decreased significantly over time, from 1608 (Period I) to 744 (Period II) and then to 149 (Period III). Conclusion: The improvements of the leptospirosis control system in Guangzhou that occurred over decades were associated with a marked decrease in the number of leptospirosis cases. Guangzhou's experience can provide guidance for other countries or cities around the world facing similar challenges.

Abstract Currently, there is no effective drugs for treating clinically COVID-19 except dexamethasone. We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid (HA). As the inhibitor of HA synthesis, hymecromone is an approved prescription drug used for treating biliary spasm. Here, we aimed to investigate the relation between HA and COVID-19, and evaluate the therapeutic effects of hymecromone on COVID-19. Firstly, HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = −0.50; P

Abstract Background The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here, we present the genotype data for dengue virus serotype 2 (DENV-2) to improve understanding of this dengue epidemic. Methods We sequenced the envelope gene of DENV-2 obtained from patient serum samples and subsequently performed maximum-likelihood phylogenetic analysis using PhyMLv3.1, maximum clade credibility analysis using BEAST v.1.10.4, and selection pressure analysis using Datamonkey 2.0. Results The prevalent DENV-2 strains identified in Guangzhou region are related to those in Southeast Asian countries. In particular, the Malaysia/Indian subcontinent genotype is prevailing in Guangzhou with no apparent genotype shift having occurred over the past 20 years. However, episodic positive selection was detected at one site. Conclusions Local control of the DENV-2 epidemic in Guangzhou requires effective measures to prevent and monitor imported cases. Moreover, the shift between the Malaysia/Indian subcontinent genotype lineages, which originated at different time points, may account for the rise in DENV-2 cases in Guangzhou. Meanwhile, the low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.

IntroductionSARS-CoV-2 has ravaged the world and undergone multiple mutations during the course of the COVID-19 pandemic. On 7 April 2022, an epidemic caused by SARS-CoV-2 Omicron (BA.2) variant broke out in Guangzhou, China, one of the largest transportation and logistical hubs of the country.MethodsTo fast curtained the Omicron epidemic, based on the routine surveillance on the risk population of SARS-CoV-2 infection, we identify key places of the epidemic and implement enhanced control measures against Omicron.ResultsTransmission characteristics of the Omicron variant were analyzed for 273 confirmed cases, and key places involved in this epidemic were fully presented. The median incubation time and the generation time were 3 days, and the reproduction number Rt was sharply increased with a peak of 4.20 within 2 days. We tried an all-out effort to tackle the epidemic in key places, and the proportion of confirmed cases increased from 61.17% at Stage 2 to 88.89% at Stage 4. Through delimited risk area management, 99 cases were found, and the cases were isolated in advance for 2.61 ± 2.76 days in a lockdown zone, 0.44 ± 1.08 days in a controlled zone, and 0.27 ± 0.62 days in a precautionary zone. People assigned with yellow code accounted for 30.32% (84/277) of confirmed COVID-19 cases, and 83.33% of them were detected positive over 3 days since code assignment. For the districts outside the epicenter, the implementation duration of NPIs was much shorter compared with the Delta epidemic last year.ConclusionBy blocking out transmission risks and adjusting measures to local epidemic conditions through the all-out effort to tackle the epidemic in key places, by delimiting risk area management, and by conducting health code management of the at-risk population, the Omicron epidemic could be contained quickly.

Background: As measles vaccination coverage has increased, measles infection has shifted to the population of infants. We conducted a follow-up seroepidemiological study among mothers and their infants to evaluate measles seroprevalence and the persistence of maternal measles antibody in Shufu, Kashgar from 2018 to 2020. Methods: Maternal venous blood and cord blood was obtained among mothers and their infants at 0, 3, 5, 8, 9, and 12 months of age. An enzyme-linked immunosorbent assay was used for quantitative measurement of measles antibodies. We analyzed the correlation between maternal and neonatal measles antibodies, and antibodies persistence after infants were born. Results: The overall neonatal maternal ratio was 2.38 (95%CI: 2.05–2.71). The measles antibodies for mothers and newborns were 438.93 IU/mL (95%CI: 409.47–470.51 IU/mL) and 440.10 IU/mL (95%CI: 410.82–471.48 IU/mL), respectively. Neonatal measles antibodies were dropping after birth and then beginning to increase starting at 8 months of age. Conclusions: Infant measles antibody levels progressively declined after birth regardless of maternal measles antibody levels. Efforts should be carried out to eliminate measles.

Abstract Background An outbreak of pneumonia, COVID-19 associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and then rapidly spread to other cities. Wenzhou is located approximately 900 km from Wuhan, which was experiencing an outbreak that was severe at the time but is considered modest as the epidemic became a pandemic. We described the epidemiological characteristics of SARS-CoV-2 outside of the epicenter to help understand the transmission pattern in a mid-sized Chinese city. Methods To investigate the epidemiological and clinical characteristics of the COVID-19, we described case series of 473 patients with confirmed COVID-19 in Wenzhou, China from January 27 to March 16, 2020. We described the public health interventions of COVID-19 and evaluated the effect of interventions by the effective reproduction number (Rt). Results The median age of all patients was 47.6 years, 48.4% of whom were female. 33.8% of the patients had a history of residence in Wuhan. Fever (71.7%) and cough (43.1%) were the most common symptoms. In addition, three kinds of unconventional cases were observed, namely 4.9% asymptomatic patients, 7.6% confirmed patients who had no link to Wuhan city but contact with individuals from Wuhan without any symptoms at the time of contact, and 12.9% confirmed patients who had an unknown source of transmission. We estimated that the basic reproductive number (R0) was 2.75 (95% CI: 2.37–3.23). The Rt fluctuated within the range of 2.50 to 3.74 from January 11 to January 16 while gradually reached a peak of 3.74 on January 16. Rt gradually decreased after January 16 and decreased to 1.00 on January 30. Rt continually decreased and reached the lowest point (0.03) on February 21, 2020. Conclusion Our study presented the possibility of asymptomatic carriers affected with SARS-CoV-2, and transmission by these three kinds of unconventional patients in Wenzhou may be an important characteristic of SARS-CoV-2 transmission. The evaluation showed that a series of multifaceted interventions proved effective in controlling the epidemic of COVID-19. These findings might provide valuable examples of control policies for countries or areas in combatting the global pandemic of COVID-19.

Objective: To determine the duration of SARS-CoV-2 persistence in quarantine hotel environments. Methods: 39 Patients confirmed by RT-PCR were included. We collected clinical features, laboratory test results, smear sample information, and quarantine room information. Genome sequencing and phylogenetic analysis were conducted. We analyzed the factors associated with environmental contamination. Result: Among 39 COVID-19 cases, 10 were asymptomatic and 37 were imported from aboard. We collected 271 swab samples from environmental surfaces related to observational patients. Eighteen swab samples from seven patients were positive. The highest contamination rates occurred on cups (100%), followed by hand sink (12.82%), toilet seat and flush (7.89%), telephone (5.56%), bedside table (5.56%), and floor drain (5.41%). The results showed that environmental surface contamination was associated with the clinical cycle threshold values for patients (P = 0.01) and the sampling interval time after the cases left their rooms (P = 0.03). The duration of environmental surface contamination was associated with the wet status of the sampling site (P = 0.01). Conclusion: Our findings showed that environmental contamination might be attributed to the viral load in the respiratory tracts of patients and the sampling interval time after the cases left their rooms. Moist surfaces were more vulnerable to remaining SARS-CoV-2 RNA-positive. Our study highlights the importance of implementing strict chemical disinfection strategies in quarantine rooms.

Abstract Background Dengue fever is a mosquito-borne infectious disease that has caused major health problems. Variations in dengue virus (DENV) genes are important features of epidemic outbreaks. However, the associations of DENV genes with epidemic potential have not been extensively examined. Here, we assessed new genotype invasion of DENV-1 isolated from Guangzhou in China to evaluate associations with epidemic outbreaks. Methodology/principal findings We used DENV-1 strains isolated from sera of dengue cases from 2002 to 2016 in Guangzhou for complete genome sequencing. A neighbor-joining phylogenetic tree was constructed to elucidate the genotype characteristics and determine if new genotype invasion was correlated with major outbreaks. In our study, a new genotype invasion event was observed during each significant outbreak period in 2002–2003, 2006–2007, and 2013–2014. Genotype II was the main epidemic genotype in 2003 and before. Invasion of genotype I in 2006 caused an unusual outbreak with 765 cases (relative risk [RR] = 16.24, 95% confidence interval [CI] 12.41–21.25). At the middle and late stages of the 2013 outbreak, genotype III was introduced to Guangzhou as a new genotype invasion responsible for 37,340 cases with RR 541.73 (95% CI 417.78–702.45), after which genotypes I and III began co-circulating. Base mutations occurred after new genotype invasion, and the gene sequence of NS3 protein had the lowest average similarity ratio (99.82%), followed by the gene sequence of E protein (99.86%), as compared to the 2013 strain. Conclusions/significance Genotype replacement and co-circulation of multiple DENV-1 genotypes were observed. New genotype invasion was highly correlated with local unusual outbreaks. In addition to DENV-1 genotype I in the unprecedented outbreak in 2014, new genotype invasion by DENV-1 genotype III occurred in Guangzhou.

Objective: Hand, foot, and mouth disease (HFMD) is an important public health issue in China. Although efficacy has been demonstrated by randomized controlled trials, the evidence for effectiveness of the monovalent Enterovirus 71 (EV71) vaccine against HFMD remains unknown. This study aimed to assess the vaccine effectiveness for HFMD in Guangzhou, China. Methods: Routinely collected vaccination and HFMD surveillance data were captured from the China Information System for Disease Control and Prevention. We estimated the EV71 vaccine effectiveness using spatial ecologic and time-series analysis approaches. Results: A total of 174,002 HFMD cases under 5 years of age were reported to the Guangzhou, China surveillance system from January 2016 to December 2018. A total of 408,664 children completed a two-dose EV71 vaccination series. In an ecologic analysis, a two-dose EV71 vaccination rate above the median conferred lower HFMD risk relative to a vaccination rate below the median (ratio ratio = 0.955, 95% confidence interval (CI): 0.949, 0.962; P

During January 26–February 10, 2020, an outbreak of 2019 novel coronavirus disease in an air-conditioned restaurant in Guangzhou, China, involved 3 family clusters. The airflow direction was consistent with droplet transmission. To prevent the spread of the virus in restaurants, we recommend increasing the distance between tables and improving ventilation.

There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.

Summary: Background: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. Methods: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. Findings: Five short sequences (24–27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. Interpretation: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. Funding: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).

Abstract Background A large number of students at a school in Guangzhou city developed a sudden onset of symptoms of diarrhea and vomiting. To help control the outbreak, we conducted an epidemiological investigation to determine the causative agent, sources, role of transmission and risk factors of the infections. Methods The study population consisted of probable and confirmed cases. An active search was conducted for cases among all students, teachers and other school staff members. A case control study was carried out using standardized online questionnaires. Data were obtained regarding demographic characteristics, gastrointestinal symptoms, personal hygiene habits, history of contact with a person who had diarrhea and/or vomiting and dining locations during the past 3 days. Rectal swabs or stool samples of the cases and, food handlers, as well as environmental samples were collected to detect potential intestinal viruses and bacteria. We calculated odds ratios and 95% confidence intervals (CIs). Results A total of 157 individuals fit the definition of a probable case, including 46 with laboratory-confirmed norovirus infection between March 8 and March 22, 2018. The proportion of students who had eaten delivery food 3 days before the onset of illness in the case group was 2.69 times that in the control group (95%CI: 1.88–3.85). Intake of take-out food 3 days earlier, and exposure to similar cases 72 h before onset and case in the same dormitory were risk factors. A total of 20 rectal swab samples from students, 10 rectal swabs from food handlers and 2 environmental swab samples from the out-campus restauranttested positive for norovirus (GII, genogroup II strain). Conclusions We investigated an outbreak of norovirus infectious diarrhea. Food handling practices carry potential risk of acute gastroenteritis outbreaks owing to a lack of surveillance and supervision. Greater attention should be paid to the monitoring and supervision of food handlers in off campus restaurant to reduce the incidence of norovirus-related acute gastroenteritis associated with delivery food.

Abstract Background Dengue is the most prevalent mosquito-borne disease in the world, with China affected seriously in recent years. 65.8% of dengue cases identified in mainland China since 2005 were reported from the city of Guangzhou. Methods In this study, we described the incidence rate and distribution of dengue cases using data collected form National Notifiable Infectious Disease Reporting Information System data in Guangzhou for 2001 to 2016. All dengue cases were investigated using standardized questionnaire. Results A total of 42,469 dengue cases were reported, with an average annual incidence rate of 20.99 per 100,000 resident population. Over this time period, the incidence rate of indigenous cases increased. Dengue affected areas also expanded sharply geographically from 58.1% of communities affected during 2001–2005 to 96.4% of communities affected in 2011–2016. Overall 95.30% of the overseas imported cases were reported during March and December, while 99.79% of indigenous cases were reported during July and November. All four dengue virus serotypes were identified both in imported cases and indigenous cases. The Aedes albopictus mosquito was the only vector for dengue transmission in the area. Conclusions Guangzhou has become the dengue epicenter in mainland China. Control strategies for dengue should be adjusted to the epidemiological characteristics above and intensive study need to be conducted to explore the factors that driving the rapid increase of dengue.

Abstract Background Several epidemiological studies have suggested that optimal obesity and visceral adiposity indicators and their cut-off values to predict cardio-metabolic risks varied among different ethnic groups. However, few studies have investigated the associations of anthropometric indices with cardio-metabolic risks in Chinese Uyghur adults, and the results were inconsistent. Methods Between May and September 2016, a total of 4664 subjects aged ≥18 years old were recruited from Northwest China. Anthropometric indices and cardio-metabolic risk factors were measured by trained personnel. Partial correlation analyses and logistic regression analyses were used to evaluate the associations of anthropometric indices with cardio-metabolic risk factors. Receiver operating characteristic analysis was used to compare the abilities of different anthropometric indices to predict cardio-metabolic risk factors, and to determine the optimal cut-off values. Results The prevalence of metabolic syndrome was 39.41% in Uyghur adults from Xinjiang Uyghur Autonomous Region. Waist circumference (WC) performed better than other obesity indices in predicting the cardio-metabolic risk factors, and the optimal cut-off value of WC to diagnose metabolic syndrome risk factors was 86.50 cm for women and 90.50 cm for men. Conclusions Our study suggests that WC had the strongest predictive power for identifying cardio-metabolic risks in Xinjiang Uyghur adults. Further well-designed longitudinal studies are needed to confirm our findings.

Background: Scrub typhus was epidemic in the western Pacific Ocean area and East Asia, scrub typhus epidemic in densely populated areas in southern China. To better understand the association between meteorological variables, Southern Oscillation Index (SOI), and scrub typhus incidence in Guangzhou was benefit to the control and prevention.Methodology/Principal Findings: We collected weekly data for scrub typhus cases and meteorological variables in Guangzhou, and Southern Oscillation Index from 2006 to 2018, and used the distributed lag non-linear models to evaluate the relationships between meteorological variables, SOI and scrub typhus. The median value of each variable was set as the reference. The high-risk occupations were farmer (51.10%), house worker (17.51%), and retiree (6.29%). The non-linear relationships were observed with different lag weeks. For example, when the mean temperature was 27.7°C with1-week lag, the relative risk (RR) was highest as 1.08 (95% CI: 1.01–1.17). The risk was the highest when the relative humidity was 92.0% with 9-week lag, with the RR of 1.10 (95% CI: 1.02–1.19). For aggregate rainfall, the highest RR was 1.06 (95% CI: 1.03–1.11), when it was 83.0 mm with 4-week lag. When the SOI was 19 with 11-week lag, the highest RR was 1.06 (95% CI: 1.01–1.12). Most of the extreme effects of SOI and meteorological factors on scrub typical cases were statistically significant.Conclusion/Significance: The high-risk occupations of scrub typhus in Guangzhou were farmer, house worker, and retiree. Meteorological factors and SOI played an important role in scrub typhus occurrence in Guangzhou. Non-linear relationships were observed in almost all the variables in our study. Approximately, mean temperature, and relative humidity positively correlated to the incidence of scrub typhus, on the contrary to atmospheric pressure and weekly temperature range (WTR). Aggregate rainfall and wind velocity showed an inverse-U curve, whereas the SOI appeared the bimodal distribution. These findings can be helpful to facilitate the development of the early warning system to prevent the scrub typhus.

The dengue fever epidemic in Guangzhou may have been affected by the Coronavirus Disease 2019 (COVID-19) pandemic. The number of dengue cases dropped drastically in 2020, and there have been only 2 local cases, suggesting that dengue has not become endemic in Guangzhou.

Background: Dyslipidemia is a major risk factor for cardiovascular disease. Several studies have explored the associations of greenness with blood lipids. However, the evidence is still limited and mixed, especially in rural areas. Methods: From May to September 2016, we recruited 4735 Uyghur adults from rural areas of northwestern China. We measured levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Two satellite-derived vegetation indices — Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) — were used to estimate residential greenness levels. The associations between exposure to residential greenness and blood lipids levels and dyslipidemia prevalence were examined using the Generalized Linear Mixed Models. Results: Living in greener areas was associated with lower TG levels, higher HDL-C levels, and lower odds of hypoalphalipoproteinemia (e.g., per 0.20-unit increase in NDVI100 m was associated with 0.02 mmol/L (95% CI: 0.001, 0.03) higher levels of HDL-C and 0.87-fold (95% CI: 0.77, 0.98) lower odds of hypoalphalipoproteinemia). These associations remained in a series of sensitivity analyses. Stratified analyses showed that the associations of NDVI100 m with LDL-C and HDL-C levels were stronger in women and in participants with higher education level. Conclusions: Higher greenness exposure was beneficially associated with blood lipids among rural Uyghur population in China, especially among women or those with higher education level.

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi (O. tsutsugamushi). Orientia tsutsugamushi has various genotypes and more new strains with difference in sequences increasingly appeared. Whether the accurateness of one special nested PCR method which amplifies segment instead of entire open reading frame (ORF) sequence meets the current work of identifying new strains and classifying genotypes remains to be confirmed. And the origins and evolution of this organism have not been thoroughly elucidated. Accordingly, in this study, segments and the entire ORF of the 56-kDa type-specific antigen (TSA56) gene of O. tsutsugamushi were collected, including 209 clinically isolated strains in Guangzhou, China from 2012 to 2016 and 139 reference strains worldwide. By performing phylogenetic analysis, we proved that the accurateness of the particular PCR method which almost met detection need. This re-grouping result showed that segments perfectly represented and identified strains of Karp, Boryong, Gilliam, TA763, Kawasaki and part of Kato genotype, and this accuracy is not restricted by region and time. Sequence diversification of Shimokoshi and some Kato strains made their genotyping need to consider entire ORF sequences, but their weak recognition might not be due to recombination. The frequent genetic recombination and high point mutations contributed to genetic diversification of the TSA56 gene. Major overlapping regions of most recombination events occurred between strains of the same genotype, especially Karp and Kato genotype. And cross-genotype overlapping events occurred between Karp and Boryong/Gilliam/TA763/Kato, Kato and Kawasaki/Gilliam/TA686, Boryong and TA686, and Gilliam and Kawasaki. But Segment has quite low recombination frequency and stable mutation trend from 1943 to 2016. So segment is a relatively conserved part of the TSA56 ORF as for its stable trend of genetic diversity, and it may anchor and represent the entire TSA56 ORF gene. And genetic diversity is rejected as one potential reason for the increased incidence of scrub typhus. But an occasional recombination event created an unrecognized genotype which might be due to the breakage of VD II and AD II. Additionally, strains in Guangzhou were homologous and Karp genotype was detected as a dominant.

Environmental antibiotic resistance genes (ARGs) have received much attention, while the characteristics of ARGs carried by particulate matter (PM) as a function of urban functional region are almost unknown. In this study, ARGs carried by PM2.5 and PM10 in an urban hospital, a nearby urban community and the nearest suburban community were detected using metagenomics. In total, 643 ARG subtypes belonging to 22 different ARG types were identified. The chloramphenicol exporter gene, sul1, bacA, and lnuA were the most abundant ARG subtypes in all air samples. The hospital exhibited higher ARG abundance and richness than the nearby communities. ARG profiles depended on functional region: hospital and suburban samples clustered separately, and samples from the nearby urban community interspersed among them. The representation of multidrug and quinolone resistance genes decayed with distance from the hospital to the urban community to the suburban community, indicating that hospital PM may be a hotspot for ARGs encoding proteins conferring multidrug and quinolone resistance. Airborne ARGs carried by PM in the hospital environment were more closely associated with clinically important pathogens than were those in nearby communities. In particular, carbapenemase genes, including blaNDM, blaKPC, blaIMP, blaVIM, and blaOXA-48, were discovered in hospital PM. In the suburban community, crAssphage, a human host-specific bacteriophage, was applied to predict ARG abundance and found to be enriched due to anthropogenic pollution but showed no clear evidence for ARG selection. In the hospital and the nearby urban community, the drivers of ARGs were complex. Our results highlighted that PM ARGs were closely related to human activities and revealed a potential hotspot, which could provide new evidence for further research and consequently mitigate the formation of airborne ARGs and transfer risks.

Background: Vaccination against seasonal influenza is usually very protective. However, coverage in service workers is low due to the large population density and high turnover. The aim of this study was to document the knowledge, attitudes and practices towards the influenza vaccine among young service workers. Methods: A face-to-face interview and questionnaire were administered at the Guangzhou Center for Disease Control and Prevention (GZCDC) clinic. The questionnaires were analyzed to evaluate knowledge, attitudes and willingness to vaccinate in the service industry population. Results: Overall, the response rate was 81.37% (1035/1272). Most of the participants had faith in the efficacy (94.20%) and safety (94.88%) of the influenza vaccine. A total of 88.7% of the respondents confirmed that children needed to be vaccinated compared to other subjects, including those who work with baby and children (45.89%), elderly people (38.95%), medical staff (38.95%) and chronic disease patients (27.33%). Only 6.47% of the respondents were clearly aware of the vaccination timeframe. One-fifth of the respondents (18.16%) reported being vaccinated within the last three years, representing a low voluntary vaccination rate (23.94%) and a high irregular vaccination rate (77.13%). The primary reason for ignoring the importance of vaccination was that the respondents believed that they were strong enough to not require immunization (42.19%). In the multivariate analysis, the main determinants of the participants' willingness to continue to vaccinate were their beliefs in vaccine protection, a high education level, vaccination behavior over the last 3 years and belief in the necessity of annual vaccinations. Conclusion: Our findings provide insights into the knowledge, attitudes and practices of the service industry population prior to vaccination season in Guangzhou City. Most participants had a passive attitude toward the influenza vaccine, but there was still relatively low knowledge and implementation of the vaccine. Governments and health departments at all levels should develop a long-term strategy for fiscal subsidy policies and new health education patterns to enhance both the recognition and coverage of the influenza vaccine and to protect the citizens as a whole from infection. There is an urgent need for the pharmaceutical industries to develop a universal vaccine and to enhance the efficacy of vaccination.

COVID-19 has now spread to become a pandemic. We confirmed six Muslim pilgrims with COVID-19 among the passengers on a flight from Pakistan, following a border inspection in Guangzhou, China. We subsequently alerted home countries to prepare early in order to manage the risk from returning pilgrims. The resulting strategies of inspection and quarantine needed to cover those returning from all Muslim countries, not just Saudi Arabia.

Mumps, a common childhood disease, has a high incidence in Guangzhou city, China. It has been proven that mumps is influenced by seasonality. However, the role of meteorological factors among children is yet to be fully ascertained. This study explored the association between meteorological factors and the incidence of mumps among children in Guangzhou. Distributed lag nonlinear models were used to evaluate the correlation between meteorological factors and the incidence of mumps among children from 2014-2018. The nonlinear lag effects of some meteorological factors were detected. Mean temperature, atmospheric pressure, and relative humidity were positively correlated with mumps incidence, contrary to that of wind speed. Extreme effects of temperature, wind speed, atmospheric pressure, and relative humidity on the incidence of mumps among children in Guangzhou were evaluated in a subgroup analysis according to gender and age. Our preliminary results offered fundamental information to better understand the epidemic trends of mumps among children to develop an early warning system, and strengthen the intervention and prevention of mumps.

BackgroundNumerous urban villages (UVs) and frequent infectious disease outbreaks are major environmental and public health concerns in highly urbanized regions, especially in developing countries. However, the spatial and quantitative associations between UVs and infections remain little understood on a fine scale.Methodology and principal findingsIn this study, the relationships between reported dengue fever (DF) epidemics during 2012-2017, gross domestic product (GDP), the traffic system (road density, bus and/or subway stations), and UVs derived from high-resolution remotely sensed imagery in the central area of Guangzhou, were explored using geographically weighted regression (GWR) models based on a 1 km × 1 km grid scale. Accounting for 16.53%-18.07% of residential area and 16.84%-18.02% of population, UVs possessed 28.55%-38.24% of total reported DF cases in the core area of Guangzhou. The density of DF cases and the DF incidence rates in UVs were 1.81-3.13 and 1.82-3.06 times of that of normal construction land. Approximately 90% of the total cases were concentrated in the UVs and their buffering zones of radius ranged from 0 to 500 m. Significantly positive associations were observed between gridded DF incidence rates and UV area (r = 0.33, P = 0.000), the number of bus stops (r = 0.49, P = 0.000) and subway stations (r = 0.27, P = 0.000), and road density (r = 0.39, P = 0.000). About 60% of spatial variations in the gridded DF incidence rates were interpreted by the different variables of GDP, UVs, and bus stops integrated in GWR models.ConclusionsUVs likely acted as special transfer stations, receiving and/or exporting DF cases during epidemics. This work increases our understanding of the influences of UVs on vector-borne diseases in highly urbanized areas, supplying valuable clues to local authorities making targeted interventions for the prevention and control of DF epidemics.

In this paper, a simple and effective method for the determination of six macrolide antibiotics (MACs), including tylosin, tilmicosin, azithromycin, clarithromycin, roxithromycin, and kitasamycin, in the chicken sample using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed based on a self-built porous aromatic framework- (PAF-) based solid phase sorbent. The main parameters influencing the extraction efficiency, such as sorbent amounts, type of the eluent, pH of the sample, and the eluent volume, were evaluated. Under the optimized condition, the limits of detection were from 0.2 to 0.5 μg·kg−1. The recoveries of the method ranged from 82.1% to 101.4% with the relative standard deviations less than 11.1%. All the results demonstrated that the established method is potential for the determination of macrolide antibiotics in food safety analysis and monitoring.

BACKGROUND:The epidemic tendency of hemorrhagic fever with renal syndrome (HFRS) is on the rise in recent years in Guangzhou. This study aimed to explore the associations between meteorological factors and HFRS epidemic risk in Guangzhou for the period from 2006-2015. METHODS:We obtained data of HFRS cases in Guangzhou from the National Notifiable Disease Report System (NNDRS) during the period of 2006-2015. Meteorological data were obtained from the Guangzhou Meteorological Bureau. A negative binomial multivariable regression was used to explore the relationship between meteorological variables and HFRS. RESULTS:The annual average incidence was 0.92 per 100000, with the annual incidence ranging from 0.64/100000 in 2009 to 1.05/100000 in 2012. The monthly number of HFRS cases decreased by 5.543% (95%CI -5.564% to -5.523%) each time the temperature was increased by 1°C and the number of cases decreased by 0.075% (95%CI -0.076% to -0.074%) each time the aggregate rainfall was increased by 1 mm. We found that average temperature with a one-month lag was significantly associated with HFRS transmission. CONCLUSIONS:Meteorological factors had significant association with occurrence of HFRS in Guangzhou, Southern China. This study provides preliminary information for further studies on epidemiological prediction of HFRS and for developing an early warning system.

This study aimed to investigate the spatiotemporal clustering and socio-environmental factors associated with dengue fever (DF) incidence rates at street level in Guangzhou city, China.Spatiotemporal scan technique was applied to identify the high risk region of DF. Multiple regression model was used to identify the socio-environmental factors associated with DF infection. A Poisson regression model was employed to examine the spatiotemporal patterns in the spread of DF.Spatial clusters of DF were primarily concentrated at the southwest part of Guangzhou city. Age group (65+ years) (Odd Ratio (OR) = 1.49, 95% Confidence Interval (CI) = 1.13 to 2.03), floating population (OR = 1.09, 95% CI = 1.05 to 1.15), low-education (OR = 1.08, 95% CI = 1.01 to 1.16) and non-agriculture (OR = 1.07, 95% CI = 1.03 to 1.11) were associated with DF transmission. Poisson regression results indicated that changes in DF incidence rates were significantly associated with longitude (β = -5.08, P

We assessed the effect of closing live poultry markets in China on influenza A(H7N9) virus detection and viability. Intensive sampling was carried out before, during, and after a 2-week citywide market closure; the markets were cleaned and disinfected at the beginning of the closure period. Swab samples were collected at different sites within the markets and tested for H7N9 by real-time reverse transcription PCR and culture. During the closure, H7N9 viral RNA detection and isolation rates in retail markets decreased by 79% (95% CI 64%–88%) and 92% (95% CI 58%–98%), respectively. However, viable H7N9 virus could be cultured from wastewater samples collected up to 2 days after the market closure began. Our findings indicates that poultry workers and the general population are constantly exposed to H7N9 virus at these markets and that market closure and disinfection rapidly reduces the amount of viable virus.

Dengue is a fast spreading mosquito-borne disease that affects more than half of the population worldwide. An unprecedented outbreak happened in Guangzhou, China in 2014, which contributed 52 percent of all dengue cases that occurred in mainland China between 1990 and 2015. Our previous analysis, based on a deterministic model, concluded that the early timing of the first imported case that triggered local transmission and the excessive rainfall thereafter were the most important determinants of the large final epidemic size in 2014. However, the deterministic model did not allow us to explore the driving force of the early local transmission. Here, we expand the model to include stochastic elements and calculate the successful invasion rate of cases that entered Guangzhou at different times under different climate and intervention scenarios. The conclusion is that the higher number of imported cases in May and June was responsible for the early outbreak instead of climate. Although the excessive rainfall in 2014 did increase the success rate, this effect was offset by the low initial water level caused by interventions in late 2013. The success rate is strongly dependent on mosquito abundance during the recovery period of the imported case, since the first step of a successful invasion is infecting at least one local mosquito. The average final epidemic size of successful invasion decreases exponentially with introduction time, which means if an imported case in early summer initiates the infection process, the final number infected can be extremely large. Therefore, dengue outbreaks occurring in Thailand, Singapore, Malaysia and Vietnam in early summer merit greater attention, since the travel volumes between Guangzhou and these countries are large. As the climate changes, destroying mosquito breeding sites in Guangzhou can mitigate the detrimental effects of the probable increase in rainfall in spring and summer.

OBJECTIVES:We aimed to evaluate the relationships between climate variability, animal reservoirs and scrub typhus incidence in Southern China. METHODS:We obtained data on scrub typhus cases in Guangzhou every month from 2006 to 2014 from the Chinese communicable disease network. Time-series Poisson regression models and distributed lag nonlinear models (DLNM) were used to evaluate the relationship between risk factors and scrub typhus. RESULTS:Wavelet analysis found the incidence of scrub typhus cycled with a period of approximately 8-12 months and long-term trends with a period of approximately 24-36 months. The DLNM model shows that relative humidity, rainfall, DTR, MEI and rodent density were associated with the incidence of scrub typhus. CONCLUSIONS:Our findings suggest that the incidence scrub typhus has two main temporal cycles. Determining the reason for this trend and how it can be used for disease control and prevention requires additional research. The transmission of scrub typhus is highly dependent on climate factors and rodent density, both of which should be considered in prevention and control strategies for scrub typhus.

Hand-foot-and-mouth disease (HFMD) is becoming one of the extremely common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, it was used an ecological study plus the negative binomial regression to identify the epidemic status of HFMD and its relationship with meteorological variables. During 2008-2012, a total of 173,524 HFMD confirmed cases were reported, 12 cases of death, yielding a fatality rate of 0.69 per 10,000. The annual incidence rates from 2008 to 2012 were 60.56, 132.44, 311.40, 402.76, and 468.59 (per 100,000), respectively, showing a rapid increasing trend. Each 1 °C rise in temperature corresponded to an increase of 9.47% (95% CI 9.36% to 9.58%) in the weekly number of HFMD cases, while a one hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 7.53% (95% CI -7.60% to -7.45%). Similarly, each one percent rise in relative humidity corresponded to an increase of 1.48% or 3.3%, and a one meter per hour rise in wind speed corresponded to an increase of 2.18% or 4.57%, in the weekly number of HFMD cases, depending on the variables considered in the model. These findings revealed that epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on the incidence of HFMD.

Abstract Background Scrub typhus is an important public health problem in China, especially in Guangzhou city. Typical outbreaks of scrub typhus have been previously reported in rural areas, affecting mainly farmers. We describe an atypical outbreak of the disease with case fatalities, from a park in Haizhu District, Guangzhou, that could turn out to be a potential scrub typhus epidemic site. Methods From May 2012 to June 2012, a case–control study was conducted to identify source and risk factors of this outbreak. Reported cases of scrub typhus in Xiaogang Park were confirmed by Weil–Felix test or a nested polymerase chain reaction (NPCR). Controls were matched with their neighbors by gender and age. Multivariate conditional logistic regression was used to identify risk factors and protective factors. Results A total of 29 cases were confirmed by Weil–Felix test, including 4 deaths by both Weil–Felix test and NPCR. All patients presented with fever (100%), while 28 (96.6%) cases had eschars, 10 (34.5%) headache, 10 (34.5%) chills, 6 (20.7%) lymphadenopathy, 5 (17.2%) rash, 2 (6.9%) vomiting and 1 (3.5%) presented with conjunctival congestion. The proportion of cases with activity history in Xiaogang Park was much higher than the control group (72.4% vs 24.1%, P < 0.001), and morning exercise in park or field was also as a risk factor for scrub typhus (adjusted OR = 3.0, 95% CI: 1.1 - 8.2). Four factors were significantly associated with the risk of developing scrub typhus: sitting on the lawn (adjusted OR = 8.0, 95% CI: 1.4 - 44.5), close contact with rats (adjusted OR = 3.3, 95% CI: 1.2 -9.6), sitting near the rat holes (OR = 6.8, 95% CI: 1.2 - 38.1) and wearing long-sleeved clothing when outside (adjusted OR = 0.3, 95% CI: 0.1 - 0.7). Conclusions We confirmed an atypical outbreak of scrub typhus in a park in Guangzhou city, which has the potential to develop into an important epidemic site. This public health risk should not be neglected and requires more attention from authorities.

Targeted surveillance for influenza A(H7N9) identified 21 cases of infection with this virus in Guangzhou, China, during April 1, 2013–March 7, 2014. The spectrum of illness ranged from severe pneumonia to asymptomatic infection. Epidemiologic findings for a family cluster of 1 severe and 1 mild case suggested limited person-to-person transmission of this virus.

Cases of brucellosis were diagnosed in 3-month-old twins and their mother. An epidemiologic survey suggested that raw sheep or goat meat might be the source of Brucella melitensis infection. This finding implies that the increasing threat of brucellosis might affect low-risk persons in urban settings in China.