广东省新型冠状病毒肺炎无症状感染者流行病学特征分析

目的 对广东省首次报告为新型冠状病毒肺炎（COVID-19）无症状感染者个案流行病学特征进行分析。方法 采用追踪观察方法,对广东省2020年1月14日至3月31日首次报告为COVID-19无症状感染者的个案进行持续追踪观察,收集流行病学相关资料,分析其流行病学特征和转归及影响因素。结果 2020年1月14日至3月31日共报告325例COVID-19无症状感染者,其流行曲线与确诊病例流行曲线相似,出现两个峰,分别在1月27日至2月5日和3月17－26日。325例个案中,184例（占56.6%）后续转为确诊病例,为潜伏期无症状感染者,其年龄M为40岁,93.5%（172/184）的潜伏期无症状感染者在首次采样检测核酸阳性3 d内出现症状;141例（占43.4%）持续无症状,属于隐性感染者,占同期报告新型冠状病毒感染者的8.6%（141/1 642）,其年龄M为27岁,从首次采样检测阳性到出院时间M为14 d,90.8%（138/141）的隐性感染者在28 d内出院转集中隔离观察,从首次采样检测核酸阳性到末次采样检测阳性时间间隔最长73 d。隐性感染者关联的密切接触者检出阳性率为0.3%,潜伏期无症状感染者关联的密切接触者检出阳性率为2.2%。潜伏期无症状感染者和隐性感染者年龄、感染来源构成差异均有统计学意义（P<0.05）。高年龄组为首次报告为“COVID-19无症状感染者”转为确诊病例的危险因素,与0~19岁组比较,40~59岁、≥60岁均为无症状感染者转确诊的危险因素,OR值（95% CI）分别为2.730（1.380~5.402）和5.302（2.199~12.783）,P值分别为0.004和0.000。境内感染无症状感染者更易转为确诊病例（OR=7.121,P=0.000）。结论 新型冠状病毒感染者中存在无症状感染现象,潜伏期无症状感染者传染性可能强于隐性感染者,高年龄组、境内感染是无症状感染者转为确诊病例的危险因素,需引起关注,后续需要在人群中开展血清学调查,为防控策略制定提供依据。     

Men having sex with men and the HPV vaccine in France: A low vaccine coverage that may be due to its infrequent proposal by physicians

IntroductionIn France, the human papilloma (HPV) vaccine is recommended to all female adolescents, and since 2016 to men having sex with men (MSM) under the age of 27. Here, we aimed to explore HPV vaccine coverage in adult MSM living in France.MethodsWe elaborated an anonymous online questionnaire targeting MSM and disseminated it between October 7, 2018 and January 15, 2019 by various means, including a Facebook® discussion forum for pre-exposure prophylaxis (PrEP) users.ResultsOverall, 2094 participants completed the questionnaire (mean age 35.4 ± 11 years); 25.8% were in the age class targeted by the HPV vaccine recommendation; 16.1% were in a PrEP program. On a 1–10 scale, they evaluated being “in favor of vaccination” at a median of 10, and general vaccine usefulness and harmfulness at medians of 10 and 2, respectively; 62.4% considered that the HPV vaccine was rather not or not at all dangerous. Those using PrEP had better perceptions of vaccination in general and of the HPV vaccine in particular. For the 1728 participants with a family physician, he/she had proposed the HPV vaccine in 9.9% of cases (9.1% of those in the targeted age class [<27 years]). Overall, 1994 knew their HPV vaccine status; 8.0% had received at least 1 dose of the vaccine, including 17.9% of those in the targeted age class (and 52.2% among the 40 participants in this age group who received PrEP). When the 1935 participants who declared to be unvaccinated against HPV were asked whether they would accept to be vaccinated, 34.4% answered “rather yes” and 45.5% “definitely yes”.ConclusionHPV vaccine coverage is low among French MSM. Our results suggest that this trend has more to do with the infrequent proposals made by clinicians than with negative vaccine perceptions.     

Lower respiratory infections mortality among Brazilians under-five before and after national pneumococcal conjugate vaccine implementation

BackgroundStudies on the impact of pneumococcal conjugate vaccines (PCV) on mortality, especially among preschoolers are scarce. We aimed to assess time trend mortality from lower respiratory infections (LRI), taken as a proxy of pneumonia, from 1990 to 2017.MethodsThis ecological study assessed the mortality rate among Brazilians under-five before and after the national PCV-10 implementation in 2010. Pneumococcal meningitis (PM) and diarrheal diseases (DD) were included as a “positive and negative controls”, respectively. Trend analysis was performed through Global Burden of Disease estimates. Joinpoint regression modeling was used to describe trends in mortality and to identify time points of its statistically significant decreases throughout the study period.ResultsThere was a sustainable reduction in mortality rates for these three diseases, with no relevant changes in the secular trends for LRI and PM after the PCV-10 implementation. For LRI, PM, and DD the higher and statistically significant (p < 0.05) annual percent change reduction occurred between 2000 and 2003, (−8.3%), 1997–2000 (−11.9%), and 1990–1994.(−13.8%), respectively, i.e., several years before the nationwide implementation of PCV-10. Moreover, for LRI the annual percent change (from −5.9 to −8.8) verified from 1990 to 2009, i.e., 20 years before countrywide vaccination, was comparable to that observed during the PCV era, that is, from minus 5.8 to minus 7.8, between 2010 and 2017.ConclusionMortality from LRI, PM, and DD decreased over time, irrespective of national PCV-10 implementation in Brazil. Other factors such as healthcare delivery, socioeconomic status improvement, and health interventions may have impacted this secular trend.     

Pneumonia prevention: Cost-effectiveness analyses of two vaccines among refugee children aged under two years,Haemophilus influenzae type b-containing and pneumococcal conjugate vaccines,during a humanitarian emergency,Yida camp,South Sudan

By September 2013, war between Sudan and South Sudan resulted in >70,000 Sudanese refugees and high pneumonia incidence among the 20,000 refugees in Yida camp, South Sudan. Using Médecins Sans Frontières (MSF)-provided data and modifying our decision-tree models, we estimated if administering Haemophilus influenzae type b (Hib)-containing (pentavalent vaccine, also with diphtheria pertussis and tetanus [DPT] and hepatitis B) and pneumococcal conjugate (PCV) vaccines were cost-effective against hospitalized pneumonia. Among children <2 years old, compared with no vaccination, one- and two-doses of combined Hib-containing and PCV would avert an estimated 118 and 125 pneumonia cases, and 8.5 and 9.1 deaths, respectively. The cost per Disability-Adjusted-Life-Year averted for administering combined one- and two-doses was US$125 and US$209, respectively. MSF demonstrated that it was possible to administer these vaccines during an emergency and our analysis found it was highly cost-effective, even with just one-dose of either vaccine. Despite unknown etiology, there is strong field and now economic rationale for administering Hib and PCV during at least one humanitarian emergency.     

Expression of complete SIV p27 Gag and HIV gp120 engineered outer domains targeted by broadly neutralizing antibodies in live rubella vectors

Infection with HIV or SIV often elicits a potent immune response to viral antigens. This includes T cells and antibodies specific for Gag and Env antigens. In contrast, when given as a vaccine, the same antigens have been weak immunogens, unable to elicit antibodies with comparable titer, durability, or neutralizing activity. We have used the live attenuated rubella vaccine strain RA27/3 as a viral vector to express HIV and SIV antigens. By mimicking an HIV infection, these vectors could elicit stronger and more durable immunity to HIV antigens. The vectors are based on the licensed rubella vaccine strain, which has demonstrated safety and potency in millions of children. One or two doses protect for life against rubella infection. The question was whether rubella vectors could similarly enhance the immunogenicity of a foreign vaccine insert.We have previously reported that rubella vectors can express small protein antigens in vitro and in vivo, where they elicit a strong immune response to the vaccine insert. The vectors have now expressed larger vaccine inserts that include epitope-rich fragments of the Gag matrix and capsid proteins (aa 41-211) or the complete p27 capsid protein with p2 (aa 136-381). These vectors have elicited a robust and durable immune response to Gag in rhesus macaques. This size range also encompasses the engineered outer domain (eOD) of HIV envelope gp120 (172 amino acids). The rubella/eOD-GT6 and GT8 vectors stably expressed glycoproteins that bind germline precursors and mature forms of VRC01-class broadly neutralizing antibodies. These vectors potentially could be used as part of a sequential immunization strategy to initiate the production of broadly neutralizing antibodies.     

基于Lasso-Logistic回归构建美沙酮维持治疗门诊患者继续使用毒品风险预测模型

  目的  探讨美沙酮维持治疗(methadone maintenance treatment, MMT)门诊患者入组治疗后继续使用毒品的影响因素,构建并验证继续使用毒品风险预测模型。  方法  以2013―2017年入组云南省MMT门诊的患者为研究对象,利用Lasso回归筛选出与患者继续使用毒品相关的变量,用于构建多因素Logistic回归分析模型;采用Bootstrap法进行模型内部验证并用列线图实现模型的可视化。  结果  本研究纳入的7 899名研究对象在接受治疗的6个月内,共有4 125(52.22%)人发生了继续使用毒品行为。Lasso回归筛选出9个与继续使用毒品相关的变量,分别是男性、独居、目前无工作、家庭关系一般、家庭关系较差、吸毒时长、过去1个月有注射行为、过去3个月曾被公安抓捕和过去3个月因吸毒而违法犯罪。预测模型的曲线下面积(area under curve, AUC)为0.70(95% CI: 0.69~0.72)。  结论  本研究构建的风险预测模型具有较好的预测能力,可用于指导MMT门诊工作人员提早识别出治疗期间继续使用毒品的高风险人群。