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Background: The natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic. Aim: Our objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period. Methods: We estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period. Results: The median incubation period was 7.2 (95% confidence interval (CI): 6.9-7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2-5.3) and 4.6 (95% CI: 4.2-5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission. Conclusion: The high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

Intra-articular injection of anti-inflammatory drugs can be a promising strategy for recovery of injured articular cartilage. We prepared a series of injectable thermo-sensitive composite hydrogels, composed of Pluronic F127, glycosaminoglycan (GAG) and bone morphogenetic protein (BMP-2), which was designed to mimic extracellular matrix (ECM). The rheological properties and dissolution rate of composite hydrogels containing chondroitin sulfate or with different hyaluronic acid molecular mass (10k, 90k, 800k) were investigated. Meanwhile, bovine serum albumin (BSA) or FITC-BSA was chosen as model drug loaded into PF/GAG hydrogels to study their sustained release behavior in vitro. The results showed that hydrogels could maintain shapes for more than 16 days and the release rate of BSA in PF/GAG composite gels was much slower than in PF127 gels, due to the affinity between BSA and GAG. Furthermore, increasing the molecular weight of hyaluronic acid correspondingly increased hydrogel dissolution rate and BSA release in the hydrogels. Subsequently, MTT experiments were performed to investigate the toxicity of the hydrogels on mouse pre-osteoblast cell MC3T3-E1. In vivo anti-inflammation results showed that PF/GAG@BMP-2 composite hydrogels had the most efficient efficacy on recovery of injured cartilage, which is induced by osteoarthritis, compared to the control groups (PF127@BMP-2 or BMP-2 saline solution).

BackgroundAccording to the global framework of eliminating human rabies, China is responding to achieve the target of zero human death from dog-mediated rabies by 2030. Chongqing is the largest municipality directly under central government in China. We described the epidemiological characteristics and post-exposure prophylaxis (PEP) of human rabies in this area, in order to provide a reliable epidemiology basis for further control and prevention of human rabies.MethodsThe most updated epidemiological data for human rabies cases from 2007 to 2016 in Chongqing were collected from the National Disease Reporting Information System. A standardized questionnaire was applied to the human rabies cases or family members of cases as proxy to investigate the PEP situation.ResultsA total of 809 fatal human rabies cases were reported in Chongqing from 2007 to 2016. There was a trend of gradual annual decline about number of cases from 2007 to 2013, followed by stable levels until 2016. Rabies was mostly reported in summer and autumn; a majority of cases were noted in farmers (71.8%), especially in males (65.3%). The cases aged 35–74 and 5–14 years old accounted for 83.8% of all the cases. We collected information of 548 human rabies cases’ rabies exposure and PEP situation. Of those, 95.8% of human rabies cases were victims of dog bites or scratch, and 53.3% of these dogs were identified as stray dogs. Only 4.0% of the domestic dogs were reported to have been vaccinated previously. After exposure, 87.8% of the 548 human rabies cases did not seek any medical services. Further investigation showed that none of the 548 cases received timely and properly standardized PEP.ConclusionHuman rabies remains a major public health problem in Chongqing, China. Dogs are the main reservoir and source of human rabies infection. Unsuccessful control of canine rabies and inadequate PEP of cases might be the main factors leading to the serious human rabies epidemic in this area. An integrated “One Health” approach should be encouraged and strengthened in this area; with combined effort it would be possible to achieve the elimination of human rabies in the expected date.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2830-x) contains supplementary material, which is available to authorized users.

(1) Objective: Even with licensed vaccine for enterovirus 71 (EV71) put into market in 2016 in China, hand, foot, and mouth disease (HFMD) is still a threat for children’s health in Chongqing. We described the epidemiological characteristics and spatial–temporal patterns of HFMD in Chongqing from 2009 to 2016, in order to provide information and evidence for guiding public health response and intervention. (2) Methods: We retrieved the HFMD surveillance data from January 2009 to December 2016 from “National Disease Reporting Information System”, and then analyzed demographic and geographical information integrally. Descriptive analysis was conducted to evaluate the epidemic features of HFMD in Chongqing. The spatial–temporal methods were performed to explore the clusters at district/county level. (3) Results: A total of 276,207 HFMD cases were reported during the study period (total population incidence: 114.8 per 100,000 per year), including 641 severe cases (129 deaths). The annual incidence of HFMD sharply increased in even-numbered years, but remained stable or decreased in odd-numbered years. A semiannual seasonality was observed during April to July, and October to December in each year. The male-to-female ratios of the mild and severe cases were 1.4:1 and 1.5:1, with the median age of 2.3 years and 1.9 years, respectively. More than 90% of the cases were children equal to and less than 5 years old. High-incidence clustered regions included the main urban districts and northeast regions according to incidence rates comparison or space–time cluster analysis. A total of 19,482 specimen were collected from the reported cases and 13,277 (68.2%) were positive for enterovirus. EV71 was the major causative agent for severe cases, while other enteroviruses were the predominant serotype for mild cases. (4) Conclusions: The characteristics of HFMD in Chongqing exhibited a phenomenon of increasing incidence in two-year cycles and semiannual seasonality in time distribution. Children ≤5 years old, especially boys, were more affected by HFMD. EV71 was the major causative agent for severe cases. We suggest initiating mass EV71 vaccination campaigns among children aged 6 months to 5 years in Chongqing, especially in the main urban districts and northern regions, in order to reduce case fatality, and take integrated measurements for controlling and preventing HFMD attributed to other enteroviruses.

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Background Before effective vaccines become widely available, sufficient understanding of the impacts of climate, human movement and non-pharmaceutical interventions on the transmissibility of COVID-19 is needed but still lacking. Methods We collected by crowdsourcing a database of 11 003 COVID-19 cases from 305 cities outside Hubei Province from December 31, 2019 to April 27, 2020. We estimated the daily effective reproduction numbers ( R t ) of COVID-19 in 41 cities where the crowdsourced case data are comparable to the official surveillance data. The impacts of meteorological variables, human movement indices and nonpharmaceutical emergency responses on R t were evaluated with generalized estimation equation models. Findings The median R t was 0•46 (IQR: 0•37–0•87) in the northern cities, higher than 0•20 (IQR: 0•09–0•52) in the southern cities ( p =0•004). A higher local transmissibility of COVID-19 was associated with a low temperature, a relative humidity near 70–75%, and higher intracity and intercity human movement. An increase in temperature from 0℃ to 20℃ would reduce R t by 30% (95 CI 10–46%). A further increase to 30℃ would result in another 17% (95% CI 5–27%) reduction. An increase in relative humidity from 40% to 75% would raise the transmissibility by 47% (95% CI 9–97%), but a further increase to 90% would reduce the transmissibility by 12% (95% CI 4–19%). The decrease in intracity human movement as a part of the highest-level emergency response in China reduced the transmissibility by 36% (95% CI 27–44%), compared to 5% (95% CI 1–9%) for restricting intercity transport. Other nonpharmaceutical interventions further reduced R t by 39% (95% CI 31–47%). Interpretation Climate can affect the transmission of COVID-19 where effective interventions are implemented. Restrictions on intracity human movement may be needed in places where other nonpharmaceutical interventions are unable to mitigate local transmission. Funding China Mega-Project on Infectious Disease Prevention; U.S. National Institutes of Health and National Science Foundation.

Hand, foot, and mouth disease (HFMD) is an enterovirus-induced infectious disease, mainly affecting children under 5 years old. Outbreaks of HFMD in recent years indicate the disease interacts with both the weather and season. This study aimed to investigate the seasonal association between HFMD and weather variation in Chongqing, China. Generalized additive models and distributed lag non-linear models based on a maximum lag of 14 days, with negative binomial distribution assumed to account for overdispersion, were constructed to model the association between reporting HFMD cases from 2009 to 2014 and daily mean temperature, relative humidity, total rainfall and sun duration, adjusting for trend, season, and day of the week. The year-round temperature and relative humidity, rainfall in summer, and sun duration in winter were all significantly associated with HFMD. An inverted-U relationship was found between mean temperature and HFMD above 19 °C in summer, with a maximum morbidity at 27 °C, while the risk increased linearly with the temperature in winter. A hockey-stick association was found for relative humidity in summer with increasing risks over 60%. Heavy rainfall, relative to no rain, was found to be associated with reduced HFMD risk in summer and 2 h of sunshine could decrease the risk by 21% in winter. The present study showed meteorological variables were differentially associated with HFMD incidence in two seasons. Short-term weather variation surveillance and forecasting could be employed as an early indicator for potential HFMD outbreaks.