- 作者列表："Hellewell J","Abbott S","Gimma A","Bosse NI","Jarvis CI","Russell TW","Munday JD","Kucharski AJ","Edmunds WJ","Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group.","Funk S","Eggo RM
BACKGROUND:Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19. METHODS:We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort. FINDINGS:Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5. For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset. INTERPRETATION:In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts. FUNDING:Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.
背景: 病例隔离和接触者追踪用于控制传染病的暴发，并已用于冠状病毒疾病 2019 (新型冠状病毒肺炎)。该策略是否将实现控制取决于病原体和响应的特征。在这里，我们使用一个数学模型来评估隔离和接触者追踪是否能够控制新型冠状病毒肺炎输入病例的传播。 方法: 我们建立了一个随机传播模型，参数化到新型冠状病毒肺炎爆发。我们使用该模型量化了接触者追踪和隔离病例在控制新型冠状病毒 (SARS-CoV-2) 样病原体方面的潜在有效性。我们考虑了初始病例数量、基本再现数 (基本传染数) 、从症状发作到隔离的延迟、追踪接触者的概率、症状发作前发生的传播比例，以及亚临床感染的比例。我们假设隔离阻止了模型中所有进一步的传播。如果传播在 12 周内或总共 5000 例病例之前结束，则认为疫情得到了控制。我们测量了使用隔离和接触者追踪控制疫情的成功，并量化了每周最大追踪病例数，以衡量公共卫生工作的可行性。 结果: 从 5 例初始病例开始的模拟暴发，1 · 5 的基本传染数，症状发作前 0% 的传播可以控制，即使接触追踪概率低; 然而，当基本传染数为 2 · 5 或 3 · 5 时，控制暴发的概率随着初始病例数的减少而降低，并且在症状发作前传播更多。在不同的初始病例数量中，基本传染数为 1 · 5 的大多数情况是可控的，成功追踪的接触者不到 50%。为了控制大多数疫情，基本传染数的 70% 以上的接触者必须被追踪，对于 3 · 5 的基本传染数，90% 以上的接触者必须被追踪。当基本传染数为 1 · 5 时，症状发作和隔离之间的延迟在确定爆发是否可控方面起最大作用。对于基本传染数个 2 · 5 或 3 · 5 的值，如果有 40 个初始病例，只有当症状发作前不到 1% 的传播发生时，接触者追踪和隔离才是潜在可行的。 解读: 在大多数情况下，高效的接触者追踪和病例隔离足以在 3 个月内控制新型冠状病毒肺炎的新疫情。控制的可能性随着从症状发作到隔离的长时间延迟而降低，通过接触追踪确定的病例较少，并且增加症状前的传播。可以修改该模型，以反映最新的传播特征和更具体的疫情控制定义，以评估当地应对努力的潜在成功。 资助: Wellcome Trust，全球挑战研究基金和英国健康数据研究。
METHODS::The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.
METHODS::Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.
METHODS:OBJECTIVE:To describe the treatment of community-acquired pneumonia (CAP) in children under five years in Tanzania. METHODS:Between January and December 2017, children aged 2-59 months with chest radiography-confirmed CAP were enrolled. The parents were interviewed to collect information on the patients and home-based medication. Clinical information was derived from the patient files. Nasopharyngeal swab and blood samples were collected for isolation of the causative pathogens. Swab samples were analysed by quantitative PCR whereas blood samples were tested using BacT/Alert 3D. RESULTS:Overall, 109 children with CAP were included in this analysis. Provision of care to most children was delayed (median = 4.6 days). A quarter (26.6%) were given unprescribed/leftover antibiotics at home. Only one child had positive bacterial culture. Referrals were associated with nasopharyngeal carriage of Streptococcus pneumoniae (p = 0.003) and Haemophilus influenzae (p = 0.004). Of all admitted children, more than a quarter (n = 29) did not need to be hospitalised and inappropriately received injectable instead of oral antibiotics. CONCLUSION:We found high rates of home treatment, particularly with antibiotics. Appropriate health care was delayed for most children because of home treatment. Efforts are needed at the community level to improve awareness of antimicrobial resistance.