Introduction:The Haemophilus influenzae type b (Hib) conjugate vaccine is widely administered in China. Methods:We extracted data on Hib vaccine doses administered and adverse events following immunization (AEFI) reported between 2010 and 2021 from the Chinese National Immunization Information System (CNIIS). A descriptive analysis was conducted to examine the characteristics and incidence rates of AEFI with the Hib vaccine. Results:In China, between 2010 and 2021, a total of 52,910 AEFIs with the Hib vaccine were reported, resulting in an overall AEFI reporting rate of 38.10 per 100,000 doses. Common (typically minor) and rare (potentially serious) vaccine reactions occurred at rates of 34.71 and 2.78 per 100,000 doses, respectively. Among the common vaccine reactions, the incidences of fever (axillary temperature ≥38.6 ℃), injection site redness and swelling (>2.5 cm in diameter), and injection site induration (>2.5 cm in diameter) were 11.93, 9.69, and 3.38 per 100,000 doses, respectively. Rare vaccine reactions included anaphylactic rash, angioedema, and febrile convulsion with reported incidences of 2.42, 0.10, and 0.05 per 100,000 doses, respectively. The incidence of serious rare vaccine reactions was 0.16 per 100,000 doses. Conclusions:The reported incidence of AEFI with the Hib vaccine was low, with the occurrence of serious rare adverse reactions also being markedly low throughout the period 2010-2021 in China.

目的 分析中国流感疫苗(Influenza vaccine,InfV)疑似预防接种异常反应(Adverse events following immunization,AEFI)发生特征.方法 通过中国疾病预防控制信息系统收集2018-2019年和2019-2020年流感季InfV接种数据及AEFI报告数据,描述性分析AEFI分布特征和报告发生率.结果 两个流感季中国共报告12 383例InfV AEFI,总报告发生率为41.04/10万,其中一般反应、异常反应分别为37.41/10万、2.19/10万.一般反应中高热、局部红肿(直径＞2.5cm)、局部硬结(直径＞2.5cm)报告发生率分别为18.28/10万、5.95/10万、1.85/10万;异常反应中过敏性皮疹、热性惊厥、血管性水肿报告发生率分别为1.51/10万、0.16/10万、0.16/10万.结论 中国2018-2019年和2019-2020年流感季InfV不良反应报告水平在可接受范围内,应继续加强InfV AEFI监测,提高监测质量.

Background In early 2020, non-pharmaceutical interventions (NPIs) were implemented in China to reduce and contain the coronavirus disease 2019 (COVID-19) transmission. These NPIs might have also reduced the incidence of hand, foot, and mouth disease (HFMD). Methods The weekly numbers of HFMD cases and meteorological factors in 31 provincial capital cities and municipalities in mainland China were obtained from Chinese Center for Disease Control and Prevention (CCDC) and National Meteorological Information Center of China from 2016 to 2020. The NPI data were collected from local CDCs. The incidence rate ratios (IRRs) were calculated for the entire year of 2020, and for January-July 2020 and August -December 2020. The expected case numbers were estimated using seasonal autoregressive integrated moving average models. The relationships between kindergarten closures and incidence of HFMD were quantified using a generalized additive model. The estimated associations from all cities were pooled using a multivariate meta-regression model. Findings Stringent NPIs were widely implemented for COVID-19 control from January to July 2020, and the IRRs for HFMD were less than 1 in all 31 cities, and less than 0.1 for 23 cities. Overall, the proportion of HFMD cases reduced by 52. 9% (95% CI: 49.3-55.5%) after the implementation of kindergarten closures in 2020, and this effect was generally consistent across subgroups. Interpretation The decrease in HFMD incidence was strongly associated with the NPIs for COVID-19. HFMD epidemic peaks were either absent or delayed, and the final epidemic size was reduced. Kindergarten closure is an intervention to prevent HFMD outbreaks. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Background Hand, foot, and mouth disease (HFMD) is an important public health problem. A monovalent EV-A71 vaccine was launched in China in 2016. Previous studies showed that inactivated monovalent EV-A71 vaccines were highly efficient against HFMD associated with EV-A71 but not against HFMD with other etiologies, leading to a hypothesis that the introduction of EV-A71 vaccines might change the pathogen spectrum and epidemiological trend of HFMD. In this study, we described for the first time the changing epidemiological characteristics of HFMD after the launch of the EV-A71 vaccine. Methods We extracted individual-based epidemiological data on HFMD cases reported to the Chinese Center for Disease Control and Prevention between January 2013 and December 2019. We described the changing epidemiological characteristics of HFMD before and after vaccine launch according to the distribution of diseases characteristics (demographic, temporal, and geographical) and evaluated the potential changes in risk factors of severe patients. All analyses were stratified by the phase before and after vaccine launch, and by enterovirus serotype. Findings During 2013-2019, 15,316,710 probable cases of HFMD were reported. Of these, 787,197 (5.1%) were laboratory confirmed and 76,982 (0.5%) were severe. After the launch of the EV-A71 vaccine, the median age of HFMD patients infected with EV-A71 increased from 2.24 years (IQR:1.43, 3.56) to 2.81 years (IQR:1.58, 4.01). The proportion of patients less than 3 years of age decreased while the proportion of patients 3-5 years of age increased. There was a large decrease (60.7%) in the proportion of severe cases as well as a decline (28.3%) in HFMD patients infected with EV-A71. After the launch of the EV-A71 vaccine, the severe illness rate and mortality rate of HFMD patients in all age groups has decreased sharply, 62.20% and 83.78% respectively. The timing of the HFMD epidemic peak was delayed (1-2 months) . After the launch of EV-A71 vaccine, the risk of becoming a severe case for EV-A71 serotype was decreased, whereas that risk was instead increased for CV-A16 (from 0.17 (95% CI:0.16, 0.18) to 0.23 (95% CI:0.21, 0.25)) and other enterovirus compared to EV-A71 (from 0.38 (95% CI:0.37, 0.39) to 0.58 (95% CI:0.56, 0.61)). The longer the time from onset to diagnosis, the higher was the risk of being a severe case, but the effect size was decreased. Interpretation The introduction of the EV-A71 vaccine has effectively reduced the proportion of severe HFMD cases and mortality, but changes to the dominant serotypes should be closely monitored. Development of multivalent vaccines to avoid an increased case burden due to other enteroviruses is greatly needed. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

目的 分析中国水痘减毒活疫苗(Varicella attenuated live vaccine,VarV)疑似预防接种异常反应(Adverse events following immunization,AEFI)发生特征.方法 通过中国疾病预防控制信息系统收集2014-2020年VarV AEFI个案,描述性分析AEFI分布特征和报告发生率;采用两种比例失衡分析(Disproportionality analysis,DPA)检测异常反应可疑信号.结果 中国2014-2020年VarV AEFI年均报告发生率为297.92/100万剂(30 619例),其中一般反应、异常反应分别为257.66/100万剂(26 481例)、31.15/100万剂(3 201例).在异常反应中过敏性皮疹、血管性水肿、过敏性休克年均报告发生率分别为26.38/100万剂(2 711例)、0.67/100万剂(69例)、0.55/100万剂(57例);DPA检测显示过敏性休克可疑信号(IC025 = 1.01;PRR= 2.94,PRRL0.05 = 2.25)出现在2014-2015年.结论 中国2014-2020年VarV不良反应报告水平在可接受范围内,自2016年以来未检测到异常反应可疑信号.

Objective:To explore the characteristics of the initial clinical symptoms of coronavirus disease 2019 (COVID-19), so as to improve the identification ability of COVID-19 and prevent the disease from further spreading.Methods:A total of 559 close contacts with symptoms, reported from January 5 to April 7 2020 in five regions, were studied. The factors influencing the positive nucleic acid test of the SARS-CoV-2 and the developing into severe cases among COVID-19 cases were analyzed based on initial clinical symptoms.Results:Among 559 symptomatic close contacts, the average age was 43.54 years There were 320 positive nucleic acid cases and 239 negative nucleic acid cases. The common initial symptoms of COVID-19 cases were fever (50.31%), cough (44.69%), fatigue (14.06%) and pharynx ministry unwell (10.63%). Multivariate logistic regression analysis showed that the risk of SARS-CoV-2 nucleic acid test positive among symptomatic close contacts with underlying diseases was 2.70 times (95% CI: 1.52-4.98) as high as the risk among those without underlying diseases. The risks of SARS-CoV-2 nucleic acid test positive among close contacts with fatigue, dizziness and headache and chill as initial symptoms were 4.82 times (95% CI: 2.29-11.41), 2.59 times (95% CI: 1.09-6.84) and 9.34 times (95% CI: 1.74-173.18) as high as the risk among those without corresponding symptoms, respectively. The risk of developing into severe cases for people aged ≥60 years was 8.78 times (95% CI: 4.12-19.73) as high as the risk among those aged <60 years. The risk of developing into severe cases in males was 2.52 times (95% CI: 1.21-5.47) as high as the risk among females. The risk of COVID-19 cases with underlying diseases developing into severe cases were 3.56 times (95% CI: 1.55-8.24) as high as the risk among those without underlying diseases. The risks of developing into severe cases among cases with initial symptoms of fever and fatigue were 2.91 times (95% CI: 1.34-6.65) and 3.79 times (95% CI: 1.47-9.65) as high as the risks among those without corresponding symptoms, respectively. Conclusions:Close contacts with initial symptoms of fatigue, dizziness and headache, and chill should be alert to the risk of SARS-CoV-2 infection. Cases with initial symptoms of fever and faotigue should be alert to the risk of developing into severe cases. Awareness of seeking medical treatment among patients and the ability of case recognition should be further improved to detect the infected person in time.

Influenza endangers human health but can be prevented in part by vaccination. Assessing influenza vaccine effectiveness (VE) provides scientific evidence for developing influenza vaccination policy. We conducted a systematic review and meta-analysis of studies that evaluated influenza VE in mainland China. We searched six relevant databases as of 30 August 2019 to identify studies and used Review Manager 5.3 software to analyze the included studies. The Newcastle–Ottawa scale was used to assess the risk of publication bias. We identified 1408 publications, and after removing duplicates and screening full texts, we included 21 studies in the analyses. Studies were conducted in Beijing, Guangzhou, Suzhou, and Zhejiang province from the 2010/11 influenza season through the 2017/18 influenza season. Overall influenza VE for laboratory confirmed influenza was 36% (95% CI: 25–46%). In the subgroup analysis, VE was 45% (95% CI: 18–64%) for children 6–35 months who received one dose of influenza vaccine, and 57% (95% CI: 50–64%) who received two doses. VE was 47% (95% CI: 39–54%) for children 6 months to 8 years, and 18% (95% CI: 0–33%) for adults ≥60 years. For inpatients, VE was 21% (95% CI: −11–44%). We conclude that influenza vaccines that were used in mainland China had a moderate effectiveness, with VE being higher among children than the elderly. Influenza VE should be continuously monitored in mainland China to provide evidence for policy making and improving uptake of the influenza vaccine.

BACKGROUND:The relative contributions of asymptomatic, presymptomatic, and symptomatic transmission of severe acute respiratory syndrome coronavirus 2 have not been clearly measured, although control measures may differ in response to the risk of spread posed by different types of cases. METHODS:We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from 4 provinces and 1 municipality in China. We estimated the variation in risk of transmission over time and the severity of secondary infections by symptomatic status of the infector. RESULTS:There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included in the study. The secondary attack rates among close contacts of symptomatic and asymptomatic index cases were 4.1% (128 of 3136) and 1.1% (12 of 1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (odds ratio, 3.79; 95% confidence interval, 2.06-6.95). Approximately 25% (32 of 128) and 50% (6 of 12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. CONCLUSIONS:Asymptomatic and presymptomatic transmissions play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.

COVID-19 is an emerging infectious disease caused by SARS-CoV-2. After the infection of the virus, the host immune system is stimulated to produce multifarious specific antibodies to decrease or eliminate effects of the pathogen. Study of the specific antibodies dynamic characteristics in patients with COVID-19 is very important for the understanding and diagnosis of the disease, research and development of vaccine, and planning of prevention and control strategy. This paper reviews and summarizes the domestic and oversea research on dynamic characteristics of specific antibodies of COVID-19 patients, including the antibody producing, duration and level, and its possible influencing factors in order to improve the understanding of the immunological characteristics of COVID-19.

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23–February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient’s onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.

BACKGROUND:Enterovirus 71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) are common serotypes causing hand, foot, and mouth disease (HFMD). Analyses on the basic reproduction number (R0) of common pathogens causing HFMD are limited and there are no related studies using field data from outbreaks in mainland China. METHODS:We estimated the pathogen-specific basic reproduction number based on laboratory-confirmed HFMD outbreaks (clusters of ≥10 HFMD cases) reported to the national surveillance system between 2011 and 2018. The reproduction numbers were calculated using a mathematical model and the cumulative cases during the initial growth periods. RESULTS:This study included 539 outbreaks, of which 198 were caused by EV-A71, 316 by CV-A16, and 25 by CV-A6. All 10 417 cases involved were children. Assuming the outbreaks occurred in closed systems and the incubation period is 5 days, the median (interquartile range [IQR]) R0 estimates of EV-A71, CV-A16, and CV-A6 were 5.06 (2.81, 10.20), 4.84 (3.00, 9.00), and 5.94 (3.27, 10.00). After adjusting for seroprevalences, the R0 (IQR) estimates for EV-A71, CV-A16 (optimistic and conservative scenarios), and CV-A6 were 12.60 (7.35, 25.40), 9.29 (6.01, 19.20), 15.50 (9.77, 30.40), and 25.80 (14.20, 43.50), respectively. We did not observe changes in the R0 of EV-A71 after vaccine licensure (P = .67). CONCLUSIONS:HFMD is highly transmissible when caused by the 3 most common serotypes. In mainland China, it primarily affects young children. Although a vaccine became available in 2016, we have not yet observed any related changes in the disease dynamics.

BACKGROUND:Between mid-January and early February, provinces of mainland China outside the epicentre in Hubei province were on high alert for importations and transmission of COVID-19. Many properties of COVID-19 infection and transmission were still not yet established. METHODS:We collated and analysed data on 449 of the earliest COVID-19 cases detected outside Hubei province to make inferences about transmission dynamics and severity of infection. We analysed 64 clusters to make inferences on serial interval and potential role of pre-symptomatic transmission. RESULTS:We estimated an epidemic doubling time of 5.3 days (95% confidence interval (CI): 4.3, 6.7) and a median incubation period of 4.6 days (95% CI: 4.0, 5.2). We estimated a serial interval distribution with mean 5.7 days (95% CI: 4.7, 6.8) and standard deviation 3.5 days, and effective reproductive number was 1.98 (95% CI: 1.68, 2.35). We estimated that 32/80 (40%) of transmission events were likely to have occurred prior to symptoms onset in primary cases. Secondary cases in clusters had less severe illness on average than cluster primary cases. CONCLUSIONS:The majority of transmissions are occurring around illness onset in an infected person, and pre-symptomatic transmission does play a role. Detection of milder infections among the secondary cases may be more reflective of true disease severity.

Objective:To characterize the epidemiology of severe hand, foot and mouth disease (HFMD) in China from 2008 to 2018 and provide evidence for the prevention and control of severe HFMD.Methods:The incidence data of severe HFMD cases from 2008 to 2018 were collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze distributions, pathogen constituent and change of severe HFMD. Joinpoint regression model was used to analyze the trends of severity rate, proportion of severe cases and severe fatality rate.Results:From 2008 to 2018, a total of 157 065 cases of severe HFMD were reported in China, with an average annual case-severity rate of 1.05/100 000, a severe case proportion of 0.76 % and a severity-fatality rate of 2.34 %. The severity rate and the proportion of severe cases showed a downward trend after 2010, and severe fatality rate decreased significantly after 2014. The severe cases mainly occurred in infants aged ≤3 years (91.47 %), more boys were affected than girls (1.78∶1). The median age of severe HFMD cases caused by EV-A71 was highest (1.99 years) and increased year by year, other enterovirus infection cases accounted for a higher proportion in infants aged ≤1 year (66.56 %). The incidence peak occurred during April-July, other enteroviruses replaced EV-A71 as the predominant serotype in 2018 (61.97 %). The incidence of severe HFMD were high in some provinces in southwestern, central and eastern China. Conclusion:The overall severity rate, proportion of severe cases and severe fatality rate of HFMD in the mainland of China have shown a downward trend. The predominant pathogen in some provinces has changed from EV-A71 to other enteroviruses. It is necessary to strengthen the prevention and control of HFMD in key population, high incidence seasons and areas and carry out the surveillance of various pathogens of HFMD.

Objective: To understand the epidemiological characteristics and risk factors of fatal cases of hand, foot, and mouth disease (HFMD) in children under 5 years old in China from 2008 to 2018, and provide evidence for the development of targeted prevention and control measures and reduction of the incidence of fatal HFMD cases. Methods: The incidence data of reported HFMD cases in China during 2008-2018 were collected from the National Notifiable Disease Surveillance Reporting System of China for the analyses on the demographic characteristics, spatial distribution, diagnosis or reporting and pathogen spectrum of the HFMD cases. Then the risk factors causing deaths were analyzed by using logistic regression model. Results: From 2008 to 2018, a total of 3 646 fatal cases of HFMD in children under 5 years old were reported in China. There were more fatal HFMD cases in boys than in girls (1.82∶1), the death mainly occurred in age group 0 to 2 years (87.71%). Adjusted mortality rate of HFMD in children under 5 years old in China declined from 0.87 per 100 000 in 2010 to 0.11 per 100 000 in 2018 (APC=-23.20%). In the 2 523 laboratory-confirmed deaths, 2 323 (92.07%) were EV-A71 infections, but the constituents of CV-A16 and other enterovirus infections increased. The interval from onset to diagnosis M=2(P(25)-P(75):2-4)d. The interval from onset to death M=3(P(25)-P(75):2-4)d. Age between 0 and 1 years, EV-A71 infection, longer interval between onset and diagnosis, and living in rural area were the risk factors causing fatal HFMD cases. Conclusions: The number of the fatal cases, the rate of mortality and case fatality HFMD in China had shown downward trends since 2010. EV-A71 is still the main pathogen causing fatal cases, but we should pay more attention to gene pattern of the other enteroviruses except EV-A71 and CV-A16. To reduce the risk of the fatal cases we should strengthen the health education about the immunization of EV-A71 inactivated vaccines and reduce the interval from onset to diagnosis in young children in western provinces and rural areas.

Objective: To evaluate the incidence intensity of hand, foot, and mouth disease (HFMD) in 2018/2019 season in southern China by Moving Epidemic Method (MEM), and compare the intensity among provinces, so as to provide basis for optimizing the allocation of public health resources. Methods: The weekly incidence data of HFMD of children under 5 years old in 15 provinces of southern China from March 1, 2012 to February 28, 2019 were collected from Disease Surveillance Reporting System of Chinese Center for Disease Control and Prevention, and the epidemic intensity threshold of each province in southern China during this period was calculated and evaluated by MEM. Results: In the first incidence peak of 2018/2019 HFMD season, in 15 provinces in the south China, 6 provinces (Jiangsu, Zhejiang, Jiangxi, Chongqing, Sichuan and Yunnan) reported very high incidence rates in children under 5 years old while Guangdong, Guangxi and Hainan provinces had low incidence level. In the second incidence peak, the incidences in 6 provinces (Shanghai, Jiangsu, Zhejiang, Chongqing, Sichuan and Yunnan) reached very high levels. The incidences in remaining provinces also reached medium or high levels. In most provinces, the thresholds in the first incidence peak were higher than those in the second incidence peak, but Chongqing and Sichuan were different. The results of model validation showed that the sensitivity and specificity of MEM were higher than 70% except for Hainan, Chongqing and Yunnan. Conclusions: For southern provinces with two incidence peaks in HFMD season, MEM can be used to determine the epidemic intensity thresholds of different incidence peaks by dividing the disease season to analyze the incidence intensity of HFMD in different stages. The epidemic intensity threshold established by MEM integrates the historical data, and the province (city) with extremely high epidemic level identified represents that the province (city) has an abnormal increase compared with the historical incidence level, which requires more attention from all areas and timely implementation of prevention and control measures.

What is already known about this topic? Enterovirus 71 (EV-A71) is the main causative pathogen for severe and fatal patients with Hand, Foot, and Mouth Disease (HFMD) in mainland China from 2008 to 2017. Non-EV-A71 and non-CV-A16 (other enterovirus) serotypes were the major causative-serotypes for mild HFMD in years of 2013, 2015, and 2017. What is added by this report? In 2018, other enterovirus serotypes replaced EV-A71 for the first time as the major cause of severe HFMD with a proportion of 70.7%. However, at the national level, only a small proportion of the other enterovirus serotypes were further identified as CV-A6 and CV-A10. What are the limitations for public health practice? Further identification of other enterovirus serotypes is highly recommended for provincial CDCs, especially for severe HFMD. Studies contributing to a multivalent vaccine for HFMD should be prioritized.

新型冠状病毒肺炎是由新型冠状病毒感染引起的急性呼吸道传染病，新型冠状病毒感染人体后，很大比例人群表现为无症状或轻微的症状，如发热、咳嗽、呼吸急促、嗅觉或味觉丧失、胃肠道症状等，一部分表现为重症，需要住院或进入重症监护室（ICU）。本文通过对新冠病毒不良结局相关的影响因素进行综述，分析人群特征、社会因素及病毒特征等与新冠肺炎不良结局的关联，为新冠肺炎疫情应对、疫情发展和医疗卫生服务需求预测、病例识别和救治策略改进提供证据支持。