Economic Burden of Hand, Foot, and Mouth Disease - Beijing Municipality, China, 2016-2019.

What is already known about this topic?: Current research regarding hand, foot, and mouth disease (HFMD) has primarily concentrated on the economic impacts, drawing from retrospective or sentinel hospital-based data. This approach often overlooks cases that were either not consulted or were misdiagnosed. What is added by this report?: This research systematically examined the iceberg phenomenon of HFMD and its economic implications in Beijing. Our findings indicate that each confirmed case represents 9.1 actual infections, imposing financial burdens of 25.58 United States dollars (USD) per unconsulted individual, 265.75 USD per misdiagnosed individual, 366.50 USD per individual with mild cases, and 2355.89 USD per individual with severe cases. The annual economic losses attributed to HFMD in the area range from 7.03 million USD to 13.31 million USD. What are the implications for public health practice?: This study offers insight into the actual prevalence of HFMD in Beijing, as well as conducting an economic burden analysis on a per-case, per-category basis. This could facilitate a cost-effectiveness analysis of prevention and control strategies for HFMD.

Phylogenetics and phylogeographic characteristics of coxsackievirus A16 in hand foot and mouth disease and herpangina cases collected in Beijing, China from 2019 to 2021.

Coxsackievirus A16 (CV-A16) is a significant pathogen responsible for causing hand foot and mouth disease (HFMD) and herpangina (HA). This study aimed to investigate the recent evolution and spread of CV-A16 by monitoring HFMD and HA cases in 29 hospitals across 16 districts in Beijing from 2019 to 2021. The first five cases of HFMD and the first five cases of HA each month in each hospital were included in the study. Real-time reverse transcription polymerase chain reaction was used to identify CV-A16, CV-A6, and EV-A71. From each district, two to four CV-A16 positive samples with a relatively long sampling time interval every month were selected for sequencing. A total of 3344 HFMD cases and 2704 HA cases were enrolled in this study, with 76.0% (2541/3344) of HFMD and 45.4% (1227/2704) of HA cases confirmed to be infected by enterovirus. Among the EV-positive samples, CV-A16 virus was detected in 33.61% (854/2541) of HFMD cases and 13.4% (165/1227) of HA cases, with the predominant cluster being B1a. Both B1a and B1b had a co-circulation of local and imported strains, with different origin time (1993 vs. 1995), different global distribution (14 countries vs. 10 countries), and different transmission centers but mainly distributed in the southern and eastern regions of Beijing. Strengthening surveillance of HFMD in southern and eastern regions will improve the prevention and control efficiency of enterovirus infections.

Incidence and trends of 17 notifiable bacterial infectious diseases in China, 2004-2019.

BACKGROUND: Certain bacterial infectious diseases are categorized as notifiable infectious diseases in China. Understanding the time-varying epidemiology of bacterial infections diseases can provide scientific evidence to inform prevention and control measures. METHODS: Yearly incidence data for all 17 major notifiable bacterial infectious diseases (BIDs) at the province level were obtained from the National Notifiable Infectious Disease Reporting Information System in China between 2004 and 2019. Of them 16 BIDs are divided into four categories, respiratory transmitted diseases (RTDs, 6 diseases), direct contact/fecal-oral transmitted diseases (DCFTDs, 3 diseases), blood-borne/sexually transmitted diseases (BSTDs, 2 diseases), and zoonotic and vector-borne diseases (ZVDs, 5 diseases), and neonatal tetanus is excluded in the analysis. We characterized the demographic, temporal, and geographical features of the BIDs and examined their changing trends using a joinpoint regression analysis. RESULTS: During 2004‒2019, 28 779 thousand cases of BIDs were reported, with an annualized incidence rate of 134.00 per 100 000. RTDs were the most commonly reported BIDs, accounting for 57.02% of the cases (16 410 639/28 779 000). Average annual percent changes (AAPC) in incidence were - 1.98% for RTDs, - 11.66% for DCFTDs, 4.74% for BSTDs, and 4.46% for ZVDs. Females had a higher incidence of syphilis than males, and other BIDs were more commonly reported in males. Among 0-5-year-olds, the diseases with the largest increases in incidence were pertussis (15.17% AAPC) and scarlet fever (12.05%). Children and students had the highest incidence rates of scarlet fever, pertussis, meningococcal meningitis, and bacillary dysentery. Northwest China had the highest incidence of RTDs, while South and East China had the highest incidences of BSTDs. Laboratory confirmation of BIDs increased from 43.80 to 64.04% during the study period. CONCLUSIONS: RTDs and DCFTDs decreased from 2004 to 2019 in China, while BSTDs and ZVDs increased during the same period. Great attention should be paid to BSTDs and ZVDs, active surveillance should be strengthened, and timely control measures should be adopted to reduce the incidence.

A Retrospective Modeling Study of the Targeted Non-Pharmaceutical Interventions During the Xinfadi Outbreak in the Early Stage of the COVID-19 Pandemic - Beijing, China, 2020.

What is already known about this topic?: China has repeatedly contained multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks through a comprehensive set of targeted non-pharmaceutical interventions (NPIs). However, the effectiveness of such NPIs has not been systematically assessed. What is added by this report?: A multilayer deployment of case isolation, contact tracing, targeted community lockdowns, and mobility restrictions could potentially contain outbreaks caused by the SARS-CoV-2 ancestral strain, without the requirement of city-wide lockdowns. Mass testing could further aid in the efficacy and speed of containment. What are the implications for public health practice?: Pursuing containment in a timely fashion at the beginning of the pandemic, before the virus had the opportunity to spread and undergo extensive adaptive evolution, could help in averting an overall pandemic disease burden and be socioeconomically cost-effective.

SARS-CoV-2 containment was achievable during the early stage of the pandemic: a retrospective modelling study of the Xinfadi outbreak in Beijing.

Prior to the emergence of the Omicron variant, many cities in China had been able to maintain a "Zero-COVID" policy. They were able to achieve this without blanket city-wide lockdown and through widespread testing and an extensive set of nonpharmaceutical interventions (NPIs), such as mask wearing, contact tracing, and social distancing. We wanted to examine the effectiveness of such a policy in containing SARS-CoV-2 in the early stage of the pandemic. Therefore, we developed a fully stochastic, spatially structured, agent-based model of SARS-CoV-2 ancestral strain and reconstructed the Beijing Xinfadi outbreak through computational simulations. We found that screening for symptoms and among high-risk populations served as methods to discover cryptic community transmission in the early stage of the outbreak. Effective contact tracing could greatly reduce transmission. Targeted community lockdown and temporal mobility restriction could slow down the spatial spread of the virus, with much less of the population being affected. Population-wide mass testing could further improve the speed at which the outbreak is contained. Our analysis suggests that the containment of SARS-CoV-2 ancestral strains was certainly possible. Outbreak suppression and containment at the beginning of the pandemic, before the virus had the opportunity to undergo extensive adaptive evolution with increasing fitness in the human population, could be much more cost-effective in averting the overall pandemic disease burden and socioeconomic cost.

Norovirus Detection in Environmental Samples from Norovirus Outbreaks in Schools and Kindergartens - Beijing Municipality, China, October-December 2020.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: The norovirus has often caused outbreaks in schools and kindergartens, but minimal research has been performed on environmental contamination during norovirus outbreaks in schools and kindergartens. WHAT IS ADDED BY THIS REPORT?: This report conveys the norovirus detection rates and viral loads in different environmental sites in 45 norovirus outbreaks in Beijing Municipality from October to December 2020. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: The evidence presented here can instruct professionals and the public to sample and disinfect key locations of the environment purposefully when responding to norovirus outbreaks.

Evaluation of the Integrated Information System for Brucellosis Case Diagnosis and Management - Inner Mongolia Autonomous Region, China, 2019.

What is already known about this topic? Wulanchabu City Center for Endemic Disease Prevention and Control had established and used a Brucellosis Integrated Information System (BIIS) since 2013. However, it had not been systematically evaluated and promoted so far. What is added by this report? The BIIS had significantly improved the efficiency of brucellosis reporting and provided convenience for follow-up management of cases, which was valuable for finishing completely routine therapy. However, the stability of the system needs to be improved. What are the implications for public health practice? The results of the BIIS assessment demonstrated its advantages and disadvantages, which could provide some evidence for its implementation in other areas of China.

Fluorescence polarization assay improves the rapid detection of human brucellosis in China.

BACKGROUND: Brucellosis is an infectious-allergic zoonotic disease caused by bacteria of the genus Brucella. Early diagnosis is the key to preventing, treating, and controlling brucellosis. Fluorescence polarization immunoassay (FPA) is a new immunoassay for relatively rapid and accurate detection of antibodies or antigens based on antigen-antibody interaction. However, there is no report on FPA-based detection of human brucellosis in China. Therefore, this study is to evaluate the value of FPA for the diagnosis of human brucellosis in China. METHODS: We recruited 320 suspected brucellosis cases who had the clinical symptoms and epidemiological risk factors between January and December, 2019. According to China Guideline for Human Brucellosis Diagnosis, the Rose Bengal test (RBT) was used for the screening test, and the serum agglutination test (SAT) was used as the confirmatory test. Brucellosis was confirmed only if the results of both tests were positive. Additionally, FPA and enzyme linked immune sorbent assay (ELISA) were compared with SAT, and their sensitivity, specificity, coincidence rate and consistency coefficient (Kappa value) as diagnostic tests were analyzed individually and in combination. The optimal cut-off value of FPA was also determined using the receiver operator characteristic (ROC) curve. RESULTS: The optimum cut-off value of FPA was determined to be 88.5 millipolarization (mP) units, with a sensitivity of 94.5% and specificity of 100.0%. Additionally, the coincidence rate with the SAT test was 96.6%, and the Kappa value (0.9) showed excellent consistency. The sensitivity and specificity of FPA and ELISA combined were higher at 98.0% and 100.0% respectively. CONCLUSIONS: When the cut-off value of FPA test is set at 88.5 mP, it has high value for the diagnosis of brucellosis. Additionally, when FPA and ELISA are combined, the sensitivity of diagnosis is significantly improved. Thus, FPA may have potential in the future as a diagnostic method for human brucellosis in China.

Evidence for pre-symptomatic transmission of coronavirus disease 2019 (COVID-19) in China.

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.

A novel and facile immunosensor based on a barometer: Application for rapid analysis of Escherichia coli in waters.

A facile immunosensor was constructed based on a barometer indicator using a double-antibody- sandwich method for rapid and sensitive detection of Escherichia coli (E. coli) from water samples. At the present study, Anti- E. coli DH-5 polyclonal antibody was modified through enriching carboxylated magnetic beads and catalase functionalized gold nanoparticles (AuNPs)- loaded nanospheres. The functionalized AuNPs-loaded nanospheres exhibited an excellent catalysis towards decomposition of hydrogen peroxide (H2O2), generating a large volume of oxygen (O2) into waters, increasing the pressure inside the glass vial, which in turn raised the water level in barometer. Under the optimized experimental conditions, the proposed method showed wide linear ranges (102- 107 cfu mL-1), good accuracy and precision (recoveries, 86.7- 107%; CV, 3.2- 8.1%) with a limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) were 80 cfu mL-1and 267 cfu mL-1, respectively. Furthermore, the fabricated portable immunosensor device showed some distinct features in low cost and visibility, suggesting great potential for rapid and on-site analysis of this bacteria from waters in less developed areas of developing countries.

A case of brucellosis concomitant with HIV infection in China.

BACKGROUND: Human brucellosis is a neglected public health issue in China and reports of HIV-infected individuals complicated with brucellosis are rare. This report describes the case of an HIV-infected patient complicated with brucellosis. We want to raise awareness of clinical diagnosis of brucellosis among clinicians. Furthermore, we should be more concerned about cases with pyrexia of unknown origin, especially in non-epidemic areas of brucellosis in China. CASE PRESENTATION: We encountered the case of a 31-year-old HIV-infected male with a CD4+ T lymphocyte count of approximately 300. On May 1, 2019, the patient had onset of non-specific caustic irregular fever with body temperature reaching 41.0 °C. He was admitted to two medical institutions in Yunnan with pyrexia of unknown origin. Finally, on day 7 of hospitalization in the Public Health Clinical Medical Center in Chengdu City, he was diagnosed as having brucellosis infection based on blood culture results. CONCLUSIONS: This is the first reported case of brucellosis concomitant with HIV infection in China. Laboratories in infectious disease hospitals and category A level III hospitals in the southern provinces of China should be equipped with reagents for clinical diagnosis of brucellosis and to strengthen the awareness of brucellosis diagnosis in China. Secondly, in provinces with a high incidence of AIDS and brucellosis such as Xinjiang and Henan, it is recommended to implement a joint examination strategy to ensure the early detection, diagnosis, and treatment of this infection.

A competitive immunosensor for ultrasensitive detection of sulphonamides from environmental waters using silver nanoparticles decorated single-walled carbon nanohorns as labels.

A novel competitive electrochemical immunosensor based on Au nanodendrites (Au NDs)/silver nanoparticles (Ag NPs) @single-walled carbon nanohorns (SWCNHs) was established for sensitive determination of sulphonamides (SAs) in aquatic environments. The indirectly competitive binding system of the approach was composed of coating antigen that coated on Au NDs/glass carbon electrode (GCE), the target and primary antibody (Ab1). When Ab2@Ag NPs@SWCNHs was captured by coating antigen (Cag)- Ab1 complex, massive Ag+ will be released from electrode in the presence nitric acid (HNO3), consequently, the generated Ag+ will significantly amplify the electrochemical signal, which would be recorded by the linear sweep voltametry (LSV). Meanwhile, the used three-dimensional Au nanodendrites (Au NDs) could increase the conductivity of the electrode and the size of the active surface area to improve the antigen-loading. Under the optimal conditions, the immunosensor showed a good linear relationship for sulfamethazine (SMZ)ranged in 0.33-63.81 ng/mL with a detection limit of 0.12 ng/mL (LOD, based on 90% inhibition). In addition, the proposed approach exhibited satisfactory accuracy and precision (recoveries, 79.25-119.25%; CV, 2.14-9.58%), it can be applied for rapid analysis of the trace pollutants from environmental waters.

An ultrasensitive electrochemical biosensor for detection of microRNA-21 based on redox reaction of ascorbic acid/iodine and duplex-specific nuclease assisted target recycling.

A novel electrochemical biosensor was developed based on multiwall carbon nanotubes/graphene oxide nanoribbons (MWCNTs/GONRs) for sensitive analysis of microRNA-21. Signal-amplified strategy was achieved by duplex-specific nuclease assisted target recycling and alkaline phosphatase-induced redox reactions. At the fabrication process of the sensor, ssDNA capture probes were immobilized on the surface of the MWCNTs@GONRs/AuNPs modified electrode through the Au-S bond, and the streptavidin-conjugated alkaline phosphatase (SA-ALP) was attached to the end of the probe. In the absence of miRNA-21, SA-ALP catalysed the conversion of ascorbic acid 2-phosphate (AAP) into ascorbic acid (AA), triggered a redox reaction under iodine, producing a marked electrochemical response. When miRNA-21 was hybridized to the capture probe, the duplex would be cleaved by the duplex-specific nuclease (DSN), causing the electrochemical signals being significantly decreased as a result of SA-ALP detached from the electrode surface. Under the optimized conditions, our biosensor showed satisfactory sensitivity (detection limit, 0.034 fM), excellent selectivity and good accuracy (recoveries, 77.4-120.2%; RSD, 5.2-7.3%) after systematic evaluations. The proposed approach was applied to detect miRNA-21 from human serum samples, which indicated that it was reliable and could be widely used as an effective tool for rapid detection of the target in serums.

A novel electrochemical immunosensor based on catalase functionalized AuNPs-loaded self-assembled polymer nanospheres for ultrasensitive detection of tetrabromobisphenol A bis(2-hydroxyethyl) ether.

A competitive immunosensor was established using an electrochemical amperometric strategy for sensitive detection of tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE), an important derivative of tetrabromobisphenol A (TBBPA). In this system, the amplified electrochemical signal towards the reduction of hydrogen peroxide (H2O2) was recorded by amperometric method. Meanwhile, the synthetized catalase functionalized AuNPs-loaded self-assembled polymer nanospheres showed an excellent electrocatalytic ability to catalyse H2O2, which was beneficial for strengthening the electrochemical signals. Under the optimized conditions, this method displayed: (i) low detection limits (0.12 ng/mL, 7 times lower than the traditional ELISA with the same antibody); (ii) satisfactory accuracy (recoveries, 78-124%; RSD, 2.1-8.3%) and good agreement with the corresponding ELISA; (iii) low sample consumption (6 µL) and low cost. The proposed approach was applied for investigation of TBBPA-DHEE from environmental waters, and our results indicated that this immunosensor has great potential to detect the trace pollutants in aquatic environments.

Morbidity Analysis of the Notifiable Infectious Diseases in China, 2018.

What is already known about this topic? Annual morbidity analysis reports that summarized trends and changing epidemiology for notifiable diseases were published in 2013 and 2015 (1,2). What is added by this report? In 2018, the morbidity of national notifiable diseases was 559.41 per 100,000 population, an increase of 12.88% compared with the average rate between 2015-2017. The five notifiable diseases with the highest reported morbidity were hand, foot, and mouth disease (HFMD), infectious diarrhea, hepatitis B, tuberculosis, and influenza. The five regions with the highest reported morbidity of infectious diseases were Zhejiang Province, Guangxi Autonomous Region, Guangdong Province, Beijing Municipality, and Xinjiang Autonomous Region. What are the implications for public health practice? Evidence on notifiable disease morbidity trends and changing epidemiology should help disease control and prevention agencies and medical institutions direct their response and prevention efforts. In addition, this report demonstrates the continued need for surveillance systems and high-quality data to identify focal points for disease control.

A sensitive, colorimetric immunosensor based on Cu-MOFs and HRP for detection of dibutyl phthalate in environmental and food samples.

A sensitive and artful colorimetric immunosensor based on horseradish peroxidase (HRP) was designed by labelling metal-organic frameworks (Cu-MOFs) on the second antibody (Cu-MOFs@Ab2) as signal amplification for the detection of trace dibutyl phthalate (DBP). In this system, when Cu-MOFs@Ab2 was captured by antigen- primary antibody (Ab1) complex, tremendous Cu(II) will be released from Cu-MOFs in the presence of nitric acid (HNO3), and Cu(II) will be further reduced to Cu(I) after the addition of sodium ascorbate (SA), consequently, inhibiting the HRP to catalyse the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (ox TMB). Under the optimized conditions, the limit of detection (LOD) was 1 µg L-1, which was almost 60 times lower than that using a conventional ELISA with the same antibody. In addition, our method showed good accuracy and reproducibility (recoveries of 87.73-103.4%; CV values of 1.46-5.95%) through a spike-recovery analysis. The proposed immunosensor indicated great potential for trace DBP determination from environmental and food samples.

An ultrasensitive competitive immunosensor using silica nanoparticles as an enzyme carrier for simultaneous impedimetric detection of tetrabromobisphenol A bis(2-hydroxyethyl) ether and tetrabromobisphenol A mono(hydroxyethyl) ether.

Based on our produced polyclonal antibody capable of recognizing tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) and tetrabromobisphenol A mono(hydroxyethyl) ether (TBBPA-MHEE) (cross-reactivity, 100% for TBBPA DHEE; 98.7% for TBBPA MHEE), an important derivative and byproduct of tetrabromobisphenol A (TBBPA), respectively, a novel ultrasensitive competitive immunosensor was established using an electrochemical impedimetric strategy for the simultaneous detection of both chemicals. A significantly amplified electrochemical impedance spectroscopy (EIS) for quantitative target analysis was obtained through (i) the biocatalytic precipitation of 4-chloro-1-naphthol (CN) on the electrode surface triggered by horseradish peroxidase (HRP) and (ii) increased amounts of the enzyme with HRP-loaded silica nanoparticles carrying poly-brushes (SiO2@PAA) as labels, achieving a remarkable improvement in catalytic performance. Under the optimized conditions, the immunosensor showed satisfactory accuracy (recovery, 84.6-118%) and a good linear range (0.21- 111.31ng/mL) with a limit of detection (LOD) of 0.08ng/mL (S/N = 3) for TBBPA DHEE and TBBPA MHEE. In addition, the proposed approach was used to analyse real environmental water samples, and our results indicated that this immunosensor had great potential for the determination of the trace pollutants in aquatic environments.

Plasmonic ELISA Based on Nanospherical Brush-Induced Signal Amplification for the Ultrasensitive Naked-Eye Simultaneous Detection of the Typical Tetrabromobisphenol A Derivative and Byproduct.

On the basis of H2O2-mediated growth of gold nanoparticle (AuNPs), a novel plasmonic enzyme-linked immunosorbent assay (pELISA) was developed with a polyclonal antibody for the ultrasensitive simultaneous naked-eye detection of tetrabromobisphenol A bis(2-hydroxyetyl) ether (TBBPA DHEE) and tetrabromobisphenol A mono(hydroxyethyl) ether (TBBPA MHEE), one of the major derivatives and byproducts of tetrabromobisphenol A (TBBPA), respectively. In this modified indirect competitive pELISA, glucose oxidase (GOx) played an important role leading to the growth of AuNPs through a reaction between GOx and glucose to produce hydrogen peroxide (H2O2). In addition, further signal amplification was achieved via a large number of GOx molecules, which were immobilized on silica nanoparticles carrying poly brushes (SiO2@PAA) to increase the enzyme load, and the whole complex was conjugated on the second antibody. Under the optimized conditions, 10-3 µg/L TBBPA DHEE can be distinguished via the observation of a colored solution, and the limit of detection (LOD) of the method using a microplate reader reaches 3.3 × 10-4 µg/L. In contrast, the sensitivity of the method was 3 orders of magnitude higher than that using conventional colorimetric ELISA with the same antibody. Furthermore, the proposed approach showed good repeatability and reliability after a recovery test fortified with a variety of targets was performed (recoveries, 78.00-102.79%; coefficient of variation (CV), 4.38-9.87%). To our knowledge, this is the first case in which pELISA was applied for the detection of small molecules via the production of H2O2 from GOx and glucose. The method will be widely used for the investigation of TBBPA DHEE and TBBPA MHEE in real environments.