Comparative epidemiology and virology of fatal and nonfatal cases of hand, foot and mouth disease in mainland China from 2008 to 2014.

This study aimed to analyze the epidemiology and virology of fatal and nonfatal hand, foot, and mouth disease (HFMD) cases in Mainland China. A total of 10,714,237 survivors and 3046 deaths were reported from 2008 to 2014 June, with a case fatality rate of 0.03%. The morbidity of the survivors increased from 37.6/100,000 in 2008 to 139.6/100,000 in 2013 and peaked in 2012 at 166.8/100,000. However, the mortality varied around 0.03-0.04/100,000 across the time. Most of the survivors were distributed in the southern and eastern China, predominantly in the Guangxi and Hainan Province, whereas deaths were dominant in southern (Guangxi) and southwestern (Guizhou) China. The two groups showed similar seasonal fluctuations from 2008 to 2014, peaking in spring and early summer. Of the total cases, 93.97% were children less than 5 years of age, with those ≤ 2 years old accounting for 60.08% versus 84.02% in the survivor and death groups, respectively. Boys were at higher risk of infection than girls in both groups. Five years of virological surveillance showed that 43.73%, 22.04%, and 34.22% of HFMD cases were due to EV71, CoxA16 and other enteroviruses, respectively. EV71 was encountered in most deaths, with no substantial effect of age, gender, month, and year on incidence. Subgenotype C4a was the prevalent EV71 strain in Mainland China, with no significant difference in the VP1 gene related to virulence between the two groups. In conclusion, based on the largest population study, fatal and nonfatal HFMD cases, mainly caused by C4a of EV71, are circulating in Mainland China with a low-cause fatality rate.

Pandemic influenza A(H1N1) 2009 virus in pregnancy.

Two hundred fourteen abstracts and 87 full texts regarding pregnant women infected with pandemic influenza A(H1N1) 2009 virus were systematically reviewed by using a PubMed search and assessing pandemic, clinical, laboratory test, vaccine, and control experiences. Both policy and health education were excluded. This review counted the total number of pregnant cases from different countries and analyzed their epidemic features, including trimester distribution, morbidity, hospitalization, intensive care unit admissions, maternal mortality, underlying diseases, complications, high-risk factors for death, pregnancy outcome, and clinical symptoms compared with the previous pandemic seasonal influenza A/H1N1 as compared with the general population. Early identification and treatment were the most important factors in different countries and areas examined. The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study. In the future, the focus should be placed on understanding vertical transmission and the severe mechanisms.

Two adenovirus serotype 3 outbreaks associated with febrile respiratory disease and pharyngoconjunctival fever in children under 15 years of age in Hangzhou, China, during 2011.

Adenovirus serotype 3 and 7 outbreaks have occurred periodically in northern, eastern, and southern China since 1955, but there has been no report since the adenovirus serotype 7 outbreak first occurred in Hangzhou, China, in 1991. Here we explored the epidemiology and etiology of two adenovirus serotype 3 outbreaks in Hangzhou in 2011. One acute respiratory outbreak was found in Chun'an County, where a total of 371 cases were confirmed in 5 of 23 towns from 4 to 31 May 2011. The outbreak affected 18.57% (13/70) of schools and 14.49% (90/621) of classes. The incidence was 5.18% (371/7,163). The population was distributed among individuals ages 7 to 15 years. No parents or teachers were infected. Another pharyngoconjunctival fever outbreak was discovered in the Chenjinglun Swimming Center located in the Xihu District between 1 and 15 July 2011. A total of 134 cases were confirmed in 900 amateur swimmers, with an incidence of 14.89% (134/900). The ages ranged from 4 to 9 years. The two outbreaks had no severe complications or death. The viruses in 66.67% (10/15) of throat swabs from children with acute respiratory infections and 100% (10/10) of the swabs from children with pharyngoconjunctival fever were confirmed to be adenovirus serotype 3 with 100% homology by PCR. Of these samples, 60.0% (12/20) had a classical characteristic cytopathic effect, presented as grape-like clusters at 72 h after infection in HEp-2 cells. In conclusion, the acute respiratory infection and pharyngoconjunctival fever outbreak in Hangzhou were caused by the completely homologous type 3 adenovirus in subgenus B. Moreover, these outbreaks demonstrated rapid transmission rates, possibly due to close contact and droplet transmission.

Evolutionary characterization of human H1N1 influenza virus hemagglutinin genes isolated from 1947 to 2009 in China.

OBJECTIVE: Our aim was to reveal the molecular characteristics of human H1N1 influenza virus hemagglutinin (HA) genes from 1947 to 2009 in China. METHODS: 129 HA gene sequences were downloaded from NCBI's GenBank and analyzed by DNASTAR software. Additionally, the three-dimensional structure of HA protein was predicted by the SWISS-MODEL service. RESULTS: First, 2009 Chinese HA genes were 99% identical to those of Mexican and American ones; their key sites remained highly conserved. Second, 50 Chinese strains from 1947 to 2009 clustered by the year of isolation, and 2009 strains had only 70% identity to 1947-2008 ones. Third, over the past 60 years, 3 receptor-binding (RB) sites and 2 of the 8 glycosylation sites (amino acids 279 and 290) underwent considerable changes while the cleavage sites remained stable. Fourth, the human HA sequences differed completely from swine and avian isolates. Finally, the mutation of cleavage sites can change the three-dimensional structures, but single mutations cannot. CONCLUSIONS: Thus, in the past 60 years, Chinese H1N1 influenza HA genes kept stable with high affinity and low pathogenicity to human except changes in 2 glycosylation and 3 RB sites which were associated with the pandemic strength, range and host specificity of viruses.

High-resolution electron microscopy study of mesoporous dichalcogenides and their hydrogen storage properties.

In this work, we report a detailed investigation on the surface topology of ordered mesoporous WS(2) nanoarrays nanocast from the silica SBA-15 template. Using a high-resolution scanning electron microscopy (HRSEM) technique, we acquire distinguishably clear images of the WS(2) surface. A large number of small nanorods are found to be evenly distributed among the nanowire arrays, supporting their ordered mesostructures. Based on these observations, tunnel-like connecting pores are proposed to have a similar distribution in the mother mesoporous silica SBA-15 template. Interestingly, we observe the atomic crystal lattices of the layered WS(2) on the HRSEM image. To the best of our knowledge, this is the first time that atomic crystal lattices have been directly observed using a SEM technique. In addition, both materials show good adsorption-desorption capabilities with hydrogen, and the maximum amount of hydrogen that can be taken up is 0.34 wt% for mesoporous WS(2) and 0.52 wt% for mesoporous MoS(2) at a pressure of 10 bar, indicating that both are potential hydrogen storage materials.

[A five-year follow-up of one hundred and thirty-six patients of hepatitis C].

OBJECTIVE: To investigate the clinical outcome and effect of interferon treatment on patients with chronic hepatitis C. METHODS: 136 cases of patients with chronic hepatitis C were followed up by methods of retrospective survey combined with prospective study. SPSS16. 0 was used to perform chi-square test and multiple logistic regression. RESULTS: 136 cases of patients were infected with HCV virus mainly through blood and blood products transfusion. They were diagnosed mainly between 2000 and 2005. 98 cases of them had anti-viral treatment with interferon and ribavirin, while the rest did not; 12 new cases developed HCV-related cirrhosis or liver carcinoma in five years, which accounted for 8.8% of the total. Among 76 cases once treated with interferon, 46 cases (60.5%) relapsed in five years. For patients with age < 40, the rates of cirrhosis and liver cancer were 0, and patients with age ≥ 40 but < 60 years, the rates of cirrhosis and liver cancer were 12.5% (7/56 cases), while for those ≥ 60 years old the rates were 35.7% (10/28 cases). The difference was significant ( B = 0.111, Wald = 4.324, P = 0.038) as analysed by logistic regression. The rates of cirrhosis and liver cancer were zero for those with normal or within twice the upper normal AST limit in five years, 43.5% (10/23 cases) for those with AST ranging from 2 to 4 fold the upper normal limit, and 58.3% (7/12 cases) for those with AST higher than four times the upper normal limit. The difference was also significant ( B = 2.184, Wald = 5.443, P = 0.02) by logistic regression analysis. The rate of relapse was 29.7% (11/37 cases) for those using pegylated interferon and 89.7% (35/39 cases) for those using interferon. The difference was significant ( Result of logistic regression showed-B = -2.077, Wald = 4.352, P = 0.037). The rate of relapse was 100% (15/15 cases) for those with treatment less than 24 weeks, 76.2% (16/21 cases) for those with treatment more than 24 weeks but less than 48 weeks, and 37.5% (14/40 cases) for those with treatment more than 48 weeks. The difference was significant (Result of logistic regression showed-B = -1.632, Wald = 6.651, P = 0.01). 42 cases of the relapsed (91.3%) were administrated with interferon once again with ideal effect. CONCLUSION: Hepatitis C virus infection increases the risk of liver cirrhosis and liver cancer. Interferon combined with ribavirin therapy could effectively control the virus and improve outcomes. We can reduce the incidence of relapse by choosing the treatment of pegylated interferon instead of interferon and by completing the full treatment.

Clinical Characteristics of H1N1 Influenza A-Associated Mild Encephalopathy with Reversible Splenial Lesion: 4 Pediatric Cases.

OBJECTIVE: Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. METHODS: A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. RESULTS: All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. CONCLUSION: This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.

2009 pandemic characteristics and controlling experiences of influenza H1N1 virus 1 year after the inception in Hangzhou, China.

This paper described the epidemiology and controlling experiences of influenza H1N1 in Hangzhou in the past 1 year. A total of 2,078 cases confirmed by real-time quantitative PCR till March 31, 2010, were analyzed by SPSS 12.0 software. During the early pandemic stage, a patient must be tested for H1N1 nucleic acid once he/she had influenza-like symptoms with the epidemiological history in 7 days, and be diagnosed if it was positive. But in the pandemic peak, we made efforts to identify and save severe cases combined with pneumonia or hypoxemia or respiratory failure or septic shock or multiple organ dysfunctions and failure. In general, the prevalence was 2.77/100,000 (2,078/7,510,844); severity rate, 10.44% (217/2,078); fatality rate, 0.48% (10/2,078). The carrier and secondary attack rate were 9.52% (58/612) and 8.66% (53/612), respectively. About 50% of serious cases and 100% of deaths had the basic underlying diseases: cardiovascular diseases, 13.66% (25/217); chronic lung disease, 12.02% (22/217); pregnant, 7.1% (13/217). Of all cases aged from 1 month to 89 years, 52.99% (1,435/2,708) were in the 10-29 years, with most of them distributed in downtown area. The timeline showed two epidemic peaks occurred in September and November 2009, respectively. Furthermore, the hemagglutinin gene remained 99% identical with the American and vaccine strains, but only 70% with the 1947-2008 Chinese strains. In conclusion, Hangzhou pandemic influenza H1N1 was caused by the highly conserved virus, with low prevalence, transmission, and mortality, because we took efficient controlling methods.

Functional-Group Modification of Kraft Lignin for Enhanced Supercapacitors.

Recent efforts to improve the capacitances of Kraft lignin (KL) in supercapacitors have mainly focused on screening KL substrates, which could either compensate the poor conductivity of KL or directly contribute to the capacitance. However, increasing the pseudocapacitance contributed by KL itself, through hydroquinone/quinone redox cycles, remains a challenge, owing to the roughly fixed content of hydroquinone species in natural KL. In this study, the capacitance of KL is greatly improved by using a functional-group modification strategy in which methoxy groups in KL are selectively converted into phenolic hydroxy groups, which facilitate the formation of additional hydroquinone moieties and thus lead to higher pseudocapacitances. The oxidized KL materials show up to 25.6 % enhancement of the phenolic hydroxy content in comparison to raw KL, which results in 21.9 % capacitance improvement from 322 to 390 F g-1 at 0.5 A g-1 in an acidic system.

Gelated Vorinostat with inner-lysosome triggered release for tumor-targeting chemotherapy.

Histonedeacetylase inhibitor (HDACi) has great potential in targeted antitumor therapy by inhibiting tumor migration, invasion, and metastasis. As one of the typical HDACis, vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) was approved as a therapeutic agent for cancer therapy, however, challenges remain due to their poor solubility, short half-life and low efficiency in cellular penetration. Considering the disadvantages of usual drug carriers, folate and vorinostat bound BSA nanogel (FVBN)was fabricated to implement higher solubility, stability, cellular uptake, and lipase-responsive release. With good dispersion and stability, FVBN significantly increased the cellular uptake of vorinostat through folate-mediated endocytosis. FVBN exhibited comparable cytotoxicity with free SAHA, and the growth of tumor cells was blocked in G1/G0 phase just like SAHA performed in cell cycle arrest tests. Moreover, FVBN not only effectively inhibited the growth of melanoma but also observably prevented pulmonary metastasis of melanoma. In the experiment against nude mice bearing solid ovarian cancer, FVBN showed excellent antitumor effect without liver damage, demonstrating the superiority of gelated and inner-lysosome triggered release strategies to the free SAHA, and it is promising to expand the scope of application of HDACi in clinical cancer therapy.

Transmission of COVID-19 in the terminal stages of the incubation period: A familial cluster.

We report a familial cluster of 2019 novel coronavirus disease (COVID-19) to assess its potential transmission during the incubation period. The first patient in this familial cluster was identified during the presymptomatic period, as a close contact of a confirmed patient. Five family members had close contact with this first patient during his incubation period, with four of them confirmed positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the subsequent sampling tests.

A serological and molecular survey of hepatitis B in children 15 years after inception of the national hepatitis B vaccination program in eastern China.

The emergence of mutations in the hepatitis B virus (HBV) S gene has threatened the long-term success of vaccination programs since the worldwide introduction of effective vaccines against hepatitis B. This study was conducted on 5,407 children (0-8 years old) in eastern China in 2007. We analyzed the prevalence of HBsAg, anti-HBs, and "a"-determinant mutations in the HBV S gene by microparticle enzyme immunoassays, PCR, and DNASTAR software. The total HBsAg prevalence was 1.52% (82/5,407) in the children and increased with age. In contrast, the positive rate (65.42%, 2,374/3,629) and the titers of anti-HBs decreased with age. The predominant infection was HBV of genotype C and serotype adr (45/51; 88% of cases). Mutations of I126T, amino acid 137 (nt553T deletion mutation), G145A, G145R, and F158S were found in the children; the mutations of amino acid 137 and F158S have not been reported previously. The total prevalence of mutant strains was 14% (7/51). To investigate whether the infection resulted from maternal transmission, we compared the S gene sequences in 16 mother-child pairs. Fourteen mother-child pairs exhibited the same HBV genotype, with 99.5-100% sequence homology in the S gene, while two pairs exhibited different genotypes. This study suggested that the hepatitis B vaccination strategies in eastern China have been successful. Although the emergence of "a"-determinant mutations in the HBV S gene have resulted in HBV infection in immunized children, this does not pose a threat to the vaccination strategies. The HBV-infected children had contracted the infection via vertical transmission.

Influence of HBV gene heterogeneity on the failure of immunization with HBV vaccines in eastern China.

The influence of hepatitis B virus (HBV) gene heterogeneity on the failure of HBV vaccination in eastern China remains unknown. Here, we assigned 78 hepatitis B surface antigen (HBsAg)-carrier mothers to two groups: 41 mothers from whom transmission of HBV to their children was successfully prevented and 37 mothers whose children were HBsAg positive 1 year after HBV vaccination. The DNA loads in mothers of the failure group (4.17E + 07 copies/ml) were significantly higher than those in the success group (8.40E + 06 copies/ml). However, no difference was found in the S gene mutation rate and genotypes between the groups. Interestingly, Thr123Ala and Gly145Arg were observed only in failure-group mothers, whereas Thr126Asn, Thr126Ser, Thr143Asn, Asp144Gly, and Asp144Ala were seen in the success group. Thus, high viral load is an important risk factor for HBV vaccination failure, which is correlated with the positions of mutations in the S gene, but not with mutant frequencies or genotypes.

Surface Anchoring Approach for Growth of CeO2 Nanocrystals on Prussian Blue Capsules Enable Superior Lithium Storage.

Prussian blue (PB) and its analogues (PBAs) have been acknowledged as promising materials for the catalysis, energy storage, and bioapplications because of different constructions and tunable composition. The approach for surface modification with metal oxides for boosting the performance, however, is rarely reported. Herein, a facile surface anchoring strategy has been proposed to realize CeO2 nanocrystals uniformly depositing on the surface of PB. Besides, the size, thickness, and depositing density of CeO2 nanocrystals can be regulated by adjusting the amount of the precursor and the proportion of ethanol and deionized water. Furthermore, after a step of confined pyrolysis treatment under an air atmosphere, CeO2 nanocrystals with an encapsulated iron oxide structure have been obtained. This shows a remarkable cycling and rate performance when evaluated as an anode of the lithium-ion battery. The surface anchoring approach of the CeO2 nanocrystals may not only promote the various applications of PB-based materials but also provide an opportunity for developing the architecture of other CeO2-based core-shell nanostructures.

Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy.

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.

Immunotoxicity assessment of ordered mesoporous carbon nanoparticles modified with PVP/PEG.

With large surface area and three-dimensional pore structure, mesoporous carbon nanoparticles (MCN) have attracted enormous interests as potential drug carriers. However, MCN immunotoxicity has not been clarified clearly up to now. Herein we reported the effect of MCN with and without PVP or DSPE mPEG2000 (PEG) modification on immune cells including dendritic cells (DCs), T lymphocytes and RAW264.7 macrophages in vitro. Furthermore, blood biochemical tests, alexin C3 assay and histological analysis were used to investigate the toxicity of MCN in vivo. The synthesized MCN with average particle size about 90 nm was naturally insoluble in water. Surface modification with PVP (MCN-PVP) or PEG (MCN-PEG) slightly increased the particle size and Zeta potential, and effectively improved the dispersion of mesoporous carbon. MCN, MCN-PVP and MCN-PEG promoted the differentiation and maturation of the DCs, while the levels of secreted TNF-α and IL-6 were significantly suppressed by MCN-PVP and MCN-PEG. These materials significantly induced apoptosis of T lymphocytes. The histopathologic results showed that there was no significant difference between nanoparticles with or without modification. Importantly, the materials deposition was observed in the lung, which could potentially inhibit lung metastasis. In conclusion, the ordered mesoporous carbon nanoparticles superficially modified by PVP or PEG perform well in immunological biocompatibility, and are likely to be a promising candidate as medicine carrier in pharmaceutics and clinic.

Risk factors for avian influenza virus in backyard poultry flocks and environments in Zhejiang Province, China: a cross-sectional study.

BACKGROUND: Human infection of avian influenza virus (AIV) remains a great concern. Although live poultry markets are believed to be associated with human infections, ever more infections have been reported in rural areas with backyard poultry, especially in the fifth epidemic of H7N9. However, limited information is available on backyard poultry infection and surrounding environmental contamination. METHODS: Two surveillance systems and a field survey were used to collect data and samples in Zhejiang Province. In total, 4538 samples were collected by surveillance systems and 3171 from the field survey between May 2015 and May 2017, while 352 backyard poultry owners were interviewed in May 2017 by questionnaire to investigate factors influencing the prevalence of avian influenza A virus and other AIV subtypes. RT-PCR was used to test the nucleic acids of viruses. ArcGIS 10.1 software was used to generate maps. Univariate and logistic regression analyses were conducted to identify risk factors for AIV infection. RESULTS: Of the 428 poultry premises observed by the surveillance system, 53 (12.38%) were positive for influenza A virus. Of the 352 samples from poultry premises observed by field survey, 13 (3.39%) were positive for influenza A virus. The prevalence of AIV was unevenly distributed and the dominant subtype differed among cities. Eastern (Shaoxing and Ningbo) and southern (Wenzhou) cities exhibited a higher prevalence of AIV (16.33, 8.94, and 7.30% respectively). Contamination of AIV subtypes was most severe in January, especially in 2016 (23.26%, 70/301). The positive rate of subtype H5/H7/H9 was 2.53% (115/4538). Subtype H5 was the least prevalent, while subtypes H7 and H9 had similar positivity rates (1.50 and 1.32% respectively). Poultry flocks and environmental samples had a similar prevalence of AIV (4.46% vs 5.06%). The type of live birds was a risk factor and the sanitary condition of the setting was a protective factor against influenza A contamination. CONCLUSIONS: AIV subtypes were prevalent in backyard poultry flocks and surrounding environments in Zhejiang Province. The types of live birds and sanitary conditions of the environment were associated with influenza A contamination. These findings shine a light on the characteristics of contamination of AIV subtypes and emphasize the importance of reducing AIV circulation in backyard poultry settings.

Resurgence of scarlet fever in China: a 13-year population-based surveillance study.

BACKGROUND: A re-emergence of scarlet fever has been noted in Hong Kong, South Korea, and England, UK, since 2008. China also had a sudden increase in the incidence of the disease in 2011. In this study, we aimed to assess the epidemiological changes before and after the upsurge. We also aimed to explore the reasons for the upsurge in disease in 2011, the epidemiological factors that contributed to it, and assess how these could be managed to prevent future epidemics. METHODS: In this observational study, we extracted the epidemiological data for all cases of scarlet fever between 2004 and 2016 in China from the Chinese Public Health Science Data Center, the official website of National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System. These data had been collected from 31 provinces and regions in China and included geographical, seasonal, and patient demographic information. We used descriptive statistical methods and joinpoint regression to examine the spatiotemporal patterns and annual percentage change in incidence of the upsurge of disease across China. FINDINGS: Between Jan 1, 2004, and Dec 31, 2016, 502 723 cases of scarlet fever, with ten fatalities, were reported in China, resulting in an annualised average incidence of 2·8807 per 100 000 people. The annual average incidence increased from 1·457 per 100 000 people in 2004 to 4·7638 per 100 000 people in 2011 (incidence rate ratio [IRR] 3·27, 95% CI 3·22-3·32; p<0·0001), peaking in 2015 (5·0092 per 100 000 people). The annual incidence after the 2011 upsurge of scarlet fever, between 2011 and 2016, was twice the average annual incidence reported between 2004 and 2010 (4·0125 vs 1·9105 per 100 000 people; IRR 2·07, 95% CI 2·06-2·09; p<0·0001). Most cases were distributed in the north, northeast, and northwest of the country. Semi-annual patterns were observed in May-June and November-December. The median age at onset of disease was 6 years, with the annual highest incidence observed in children aged 6 years (49·4675 per 100 000 people). The incidence among boys and men was 1·54 greater than that among girls and women before the upsurge, and 1·51 times greater after the upsurge (p<0·0001 for both). The median time from disease onset to reporting of the disease was shorter after the upsurge in disease than before (3 days vs 4 days; p=0·001). INTERPRETATION: To our knowledge, this is the largest epidemiological study of scarlet fever worldwide. The patterns of infection across the country were similar before and after the 2011 upsurge, but the incidence of disease was substantially higher after 2011. Prevention and control strategies being implemented in response to this threat include improving disease surveillance and emergency response systems. In particular, the school absenteeism and symptom monitoring and early-warning system will contribute to the early diagnosis and report of the scarlet fever. This approach will help combat scarlet fever and other childhood infectious diseases in China. FUNDING: National Key R&D Plan of China Science and key epidemiological disciplines of Zhejiang Provincial Health of China.