老年糖尿病患者肺炎球菌多糖疫苗接种意愿及影响因素分析

目的 探析老年糖尿病患者肺炎球菌多糖疫苗接种意愿及影响因素。方法 以2019年4月至2020年4月上海市某医院健康服务中心定期体检的老年糖尿病患者为调查对象。设计《PPV23肺炎疫苗接种意愿调查表》,调查老年患者基本情况及PPV23肺炎疫苗接种意愿,采用多因素Logistic回归分析老年患者PPV23肺炎疫苗接种意愿的影响因素。结果 本研究共调查1 240例老年患者,平均年龄（68.35±5.13）岁,其中546例（占44.03%）愿意接种PPV23肺炎疫苗。多因素分析结果显示年龄越小（OR=4.346）、家人最高学历越高（OR_{高中或中专}=2.269,OR_{大专及以上}= 2.173）、有慢性呼吸道疾病史（OR=2.548）、认为肺炎为严重疾病（OR=1.756）、担心自身患肺炎疾病（OR=1.861）、知晓PPV23肺炎疫苗接种可预防肺炎（OR=2.085）、家人患有慢性呼吸道疾病（OR=4.166）、家人或朋友推荐接种PPV23肺炎疫苗（OR=3.572）、医生建议接种PPV23肺炎疫苗（OR=2.604）的老年糖尿病患者愿意接种PPV23肺炎疫苗的可能性越大。结论 老年糖尿病患者PPV23肺炎疫苗接种意愿较低,年龄、慢性呼吸道疾病史、肺炎及疫苗相关知识与医生建议是影响其接种意愿的相关因素。建议加强肺炎疫苗预防效果、安全性的宣传教育,提高老年糖尿病患者对PPV23肺炎疫苗的认知度。     

怀化市医疗机构工作人员新型冠状病毒疫苗接种意愿及影响因素

目的 了解怀化市医疗机构工作人员新型冠状病毒疫苗(简称新冠疫苗)接种意愿及影响因素,为新冠疫苗的接种工作提供依据。 方法 采用多阶段分层抽样法选取怀化市市、县/区、乡镇三级23家医疗机构的工作人员,开展网络问卷调查;采用χ²检验、logistic回归分析其影响因素。 结果 3 392名(85.70%)调查对象愿意接种新冠疫苗;logistic回归分析显示,乡镇级、县级医疗机构调查对象、临床医生、护理人员的接种意愿更高[OR(95%CI):1.558(1.148~2.114)、1.386(1.112~1.726)、1.550(1.008~2.384)、1.747(1.165~2.618)];硕士及以上学历者接种意愿更低[OR(95%CI):0.446(0.243~0.816)];认为新冠肺炎危害严重、认可疫苗的安全性、有效性、在 2020年接种过流感疫苗者更愿意接种新冠疫苗[OR(95%CI):1.493(1.221~1.825)、2.134(1.669~2.728)、2.546(1.925~3.366)、2.185(1.287~3.709)]。 结论 怀化市医疗机构工作人员新冠疫苗的接种意愿总体较高,应加强新冠疫苗相关知识宣传,增强该人群对疫苗接种的信心,进一步提高新冠疫苗的实际接种率。     

HIV感染者接种23价肺炎链球菌多糖疫苗的免疫效果

【目的】分析人类免疫缺陷病毒(HIV)感染者接种23价肺炎链球菌多糖疫苗(PPV23)后功能性抗体和社区获得性肺炎(CAP)发病保护效果。【方法】2015年在上海市虹口区随机选择成人HIV感染者63人,采集接种PPV23前后1个月的血标本,用肺炎链球菌荚膜多糖特异性抗体调理吞噬杀菌试验(OPA)检测4个血清型(19F、19A、23F、6B)肺炎链球菌的功能性抗体;同时调查人群接种PPV23后的CAP发病情况。【结果】HIV感染者接种PPV23后1个月的4个血清型OPA抗体几何平均滴度(GMT)显著高于接种前;HIV感染者接种后4个血清型OPA抗体≥3倍增长率分别为50%～91.67%;HIV感染者接种PPV23后与接种前自身和对照组比较,接种后2年的肺炎发病保护率均为100%。接受高效抗逆转录病毒治疗(HAART)或CD4+计数≥300/μL的HIV感染者接种PPV23后能较好地产生OPA抗体,并获得对社区获得性肺炎(CAP)的保护。【结论】建议对基本情况良好的HIV感染者常规接种PPV23。     

2017年海阳市大学新生戊型肝炎知识态度调查

目的 调查2017年海阳市大学新生对戊型肝炎(戊肝)认知情况,为制定戊肝防控策略提供依据。方法 对2017年海阳市某大学入学2 100名新生进行调查。结果 18.1％(380/2100 )的大学生知道戊肝,9.0％(189/ 2 100)的大学生对戊肝认知正确。51.0％(1 071/2 100)的大学生认为戊肝可以接种疫苗来预防, 38.7％(812/2 100 )的大学生愿意接种疫苗。结论 海阳市大学新生对戊肝知晓率较低,不良生活习惯较多,具有高感染风险 。     

一起新型冠状病毒肺炎聚集性疫情调查

目的 通过对Y市一起新型冠状病毒肺炎聚集性疫情的调查,初步分析该病潜伏期、传染期、传播能力。 方法 应用现场流行病学方法调查病例及其密切接触者,采用实时荧光RT-PCR技术对采集咽拭子标本进行新型冠状病毒核酸检测。 结果 本起疫情一共发现13名确诊病例和4名无症状感染者,发生四代病例传播,平均代际间隔时间5.08 d,平均潜伏期5.44 d(2~10 d),部分病例发病前2 d已具备传染性;密切接触者中存在一定比例隐性感染者。病例检测时存在需要多次采样检测方能确诊的现象。 结论 新型冠状病毒传播能力强,存在潜伏期传播,存在无症状感染,需加强对密切接触者的追踪、管理等防控措施。     

不同免疫策略的疑似预防接种异常反应影响分析

目的 分析辖区内相关疫苗的疑似预防接种异常反应的发生率及其他要素,给免疫规划工作人员和受种者提供客观真实的接种建议。 方法 分析2012年—2018年6月的687例疑似预防接种异常反应(AEFI)个案,AEFI以一般反应为主。 结果 单剂次疫苗的AEFI总发生率和一般反应发生率较高,各疫苗的安全性良好。 结论 为预防疫苗相关传染病,在联合疫苗及灭活疫苗供货不足的情况下,建议家长和预防接种单位工作人员尽早接种有相同预防效果的替代疫苗,提高疫苗接种的及时性。     

济南市新型冠状病毒肺炎感染者及密切接触者调查分析

目的 调查分析济南市51例新型冠状病毒肺炎(简称新冠肺炎)感染者流行病学特征及其密切接触者感染情况,为疫情防控提供科学依据。 方法 收集截至2020年3月18日济南市新冠肺炎感染者及其密切接触者的人口学、流行病学和临床资料,采用描述流行病学方法进行分析。 结果 感染者主要集中在历下区、槐荫区、市中区、长清区及天桥区,占92.16%;男女性别比为0.89∶1;年龄以30～岁年龄组最高(37.26%);普通型病例为主(70.59%);暴露史以武汉旅居史为主(43.14%);有明显的家庭聚集性(74.51%)。共有1 095人作为感染者的密切接触者纳入管理,其中15人确定感染,感染率为1.37%。不同的接触方式、与感染者关系和接触频率之间感染率差异有统计学意义(P<0.05),其中同餐同住(11.01%)、亲属关系(10.37%)及经常接触(11.43%)感染率最高。家庭密切接触者中儿童及老年人感染率较高。结论 新冠肺炎极易发生家庭内感染,对重点人群加大宣传教育及落实针对性的防护措施,对防控疫情扩散有重要意义。     

淮安地区20岁以下女性HPV疫苗接种情况及认知度调查

目的 调查淮安地区20岁以下女性HPV疫苗接种及相关认知度情况。 方法 于2020年12月1—6日采用方便抽样方法对淮安地区12～20岁以下女性展开问卷调查。问卷内容包括调查对象一般情况、HPV疫苗接种行为和意愿以及对宫颈癌及HPV疫苗认知度情况。根据调查对象对宫颈癌及HPV疫苗认知情况分为认知良好组和认知不良组,采用多因素logistic回归分析法分析影响宫颈癌及HPV疫苗认知度的影响因素。 结果 共发放问卷400份,收回有效调查问卷364份。364名调查对象中,未接种或未预约HPV疫苗接种者312名,占85.71%;已预约HPV疫苗接种者19名,占 5.22%;已接种疫苗者33名,占9.07%。312名未接种或未预约HPV疫苗接种者中,无接种意愿者76名,占24.36%;规划未来3年内接种者154名,占49.36%;规划3年后接种者82名,占26.28%。调查对象对宫颈癌及HPV疫苗认知调查问卷总分≥12分者120名,占32.97%,纳入认知良好组;得分＜12分者244名,占67.03%,纳入认知不良组。认知良好组年龄显著高于认知不良组(P＜0.05),认知良好组文化程度为高中以上、居住地区在城镇、父母职业为医学相关的占比显著高于认知不良组(P＜0.05)。多因素logistic回归性分析显示,年龄(OR=1.521,95%CI:1.108～2.088)、文化程度(OR=1.682,95%CI:1.241～2.280)、居住地区(OR=1.584,95%CI:1.141～2.199)、父母职业(OR=1.617,95%CI:1.162～2.250)是宫颈癌及HPV疫苗认知度的独立影响因素(P＜0.05)。 结论 淮安地区20岁以下女性HPV疫苗接种率和认知度较低。年龄、文化程度、居住地区、父母职业是影响HPV疫苗认知度的独立因素,因此可以针对性加强HPV疫苗接种知识宣传教育,推进宫颈癌防控工作。     

多学科专家论证川崎病儿童预防接种模式应用

目的 解决基层接种医生对患有川崎病儿童的预防接种难题。方法 采用组织临床儿科、流行病学、疫苗学等相关领域专家对川崎病儿童进行论证,形成川崎病预防接种共识建议,对符合接种建议患儿进行接种前告知,获得监护人同意后接种疫苗,进行接种疫苗后的安全性观察。结果 形成川崎病儿童的预防接种专家共识建议,分别对未发生并发症的川崎病患儿、发生并发症的患儿以及复发的川崎病患儿接种进行建议,已指导6名川崎病儿童进行疫苗接种,均未发生不良反应。结论 采用组织专家对川崎病儿童论证形成预防接种共识建议的方法,指导接种医生对患病儿童接种疫苗,可以提高该群体儿童接种率,确保接种安全,其方法安全可行。     

天津市B区一起家庭聚集性新型冠状病毒肺炎疫情调查分析

目的 分析天津市B区一起新型冠状病毒肺炎(coronavirus disease 2019, COVID-19)家庭聚集性疫情流行病学特征,为聚集性疫情的防控提供科学依据。 方法 应用现场流行病学方法调查病例及其密切接触者,采用实时荧光定量 RT-PCR 法对采集的呼吸道标本进行新型冠状病毒核酸检测。 结果 本起聚集性疫情共发现10名确诊病例和1名无症状感染者,主要以共同居住和同桌进餐等近距离接触方式传播,部分病例发病前已具备传染性,存在需多次采样检测核酸方能确诊的现象。结论 新冠肺炎家庭内传染性较强,要强化家庭成员之间防护意识,加强对无症状感染者的追踪、管理等防控措施,防止家庭聚集性疫情发生和传播。     

Evaluation of effectiveness,safety and cost-benefit of the 23– valent pneumococcal capsular polysaccharide vaccine for HIV-Infected patients

IntroductionDue to the lack of understanding of the protective effects and safety of 23-valent pneumococcal polysaccharide vaccine (PPV23) in immune-deficient populations, the vaccination rate of PPV23 among HIV-infected patients is still very low in China. The main objectives of this study were to determine whether the efforts to assess measures for the prevention of pneumococcal pneumonia are still worthwhile, and provide designated vaccination program of HIV-infected persons for government policy based on.Methods60 HIV-infected adults in Lanshan county who had never been vaccinated with any pneumococcal vaccine were enrolled in this study, voluntary vaccination of PPV23 and One-year follow-up after vaccination can be completed.Result76.67% patients (46/60) had serologic response at 12 months after vaccine, CD4 count(≤500 cells/ul or > 500 cells/ul) and Month from diagnosis to first antiviral therapy (≤1 month or > 1 month) were related to antibody responses (p < 0.05).In this study, PPV23 was well tolerated, no adverse reaction was reported.11 Streptococcus pneumoniae pneumonia (9.17%,11/120) occurred in the Unvaccinated group and 1 case(1.67%,1/60)in the vaccination group within one year after vaccination(Fisher's exact probability, P = 0.225). The VE was 81.79%. The per capita benefit was 39.32 dollars, the benefit-cost ratio = 1.19. There are significant statistical differences between the vaccinated group and the non-vaccinated group in outpatient costs (p < 0.05, 95 %CI: 9.29–32.11), Medicine costs (p = 0.017, 95 %CI: 2.47–24.44), and disease related indirect costs (p = 0.038, 95 %CI: 0.93–33.63) within one year of vaccination.ConclusionOur study results showed that PPV23 can be safely and effectively administered to HIV-1 infected individuals and effectively preventing Streptococcal pneumonia. Considering the cost-benefit of vaccination among HIV-infected persons, as it has been reported in our study, it is necessary to promote the widespread use of the vaccine among HIV-infected persons in the future.     

Economic evaluation of standing order programs for pneumococcal vaccination of hospitalized elderly patients.

BACKGROUND: Standing order programs (SOPs), which allow for vaccination without an individual physician order, are the most effective mechanism to achieve high vaccination rates. Among the suggested settings for the utilization of SOPs are hospital inpatient units, because they provide care for those most likely to benefit from vaccination. The cost-effectiveness of this approach for elderly hospitalized persons is unknown. The purpose of this study was to estimate the cost-effectiveness of SOPs for pneumococcal polysaccharide vaccine (PPV) vaccination for patients 65 years of age or older in 2 types of hospital. METHODS: In 2004, a 1,094-bed tertiary care hospital implemented a pharmacy-based SOP for PPV, and a 225-bed community hospital implemented a nursing-based SOP for PPV. Newly admitted patients 65 years of age or older were screened for PPV eligibility and then offered PPV. Vaccination rates before and after initiation of SOPs in the United States, incidence rates of invasive pneumococcal disease in the United States, and US economic data were the bases of the cost-effectiveness analyses. One-way and multivariate sensitivity analyses were conducted. RESULTS: PPV vaccination rates increased 30.5% in the tertiary care hospital and 15.3% in the community hospital. In the base-case cost-effectiveness analysis, using a societal perspective, we found that both pharmacy-based and nursing-based SOPs cost less than $10,000 per quality-adjusted life-year gained, with program costs (pharmacy-based SOPs cost $4.16 per patient screened, and nursing-based SOPs cost $4.60 per patient screened) and vaccine costs ($18.33 per dose) partially offset by potential savings from cases of invasive pneumococcal disease avoided ($12,436 per case). Sensitivity analyses showed SOPs for PPV vaccination to be cost-effective, compared with PPV vaccination without SOPs, unless the improvement in vaccination rate was less than 8%. CONCLUSION: SOPs do increase PPV vaccination rates in hospitalized elderly patients and are economically favorable, compared with PPV vaccination rates without SOPs.     

Long-lasting hyporesponsivenss induced by the 23-valent pneumococcal polysaccharide vaccine (PPV23) in asplenic patients with β-thalassemia major

We have previously shown that multiple vaccinations with 23-valent pneumococcal polysaccharide vaccine (PPV23s) resulted in attenuated antibody responses to subsequent 7-valent conjugate vaccine (PCV7) in asplenic adults with β-thalassemia major (Orthopoulos et al. Vaccine 2009; 27:350). However, there is evidence that PPV23-induced immune hyporesponsiveness could be overcome with time (Papadatou et al. Clin Infect Dis 2014; 59:862).In the current study we investigate the duration of hyporesponsiveness in the same cohort seven years after the original study vaccinations. Patients received one dose of 13-valent conjugate vaccine (PCV13) and antibody levels were measured before and one month after vaccination.Antibodies increased significantly after vaccination with PCV13, but were lower than post-PCV7 seven years earlier. Lower pre-vaccination antibody levels were associated with more robust response to PCV13.Our findings suggest that PPV23 should be used cautiously in asplenic adults vaccinated with multiple PPV23s in the past. Measurement of anti-pneumococcal antibodies before and after vaccination could be used to optimise timing of vaccinations and certify vaccine immunogenicity in such individuals.     

The cost-effectiveness of starting 23-valent pneumococcal polysaccharide vaccine and influenza vaccination at 50 vs. 65 years: A comparative modelling study

ObjectivesPneumococcal infection is a leading cause of morbidity and mortality. We aimed to evaluate the cost-effectiveness of 23-valent polysaccharide vaccine (PPV23) together with influenza vaccination or pneumococcal vaccination alone in adults starting from 50 years vs. 65 years in Hong Kong.MethodsA hypothetical population of 100,000 older adults was included in a Markov model with age ranging from 50 to 85 years to calculate the cost and quality-adjusted life-years (QALYs) gained for vaccination strategies, including: (1) annual influenza vaccine and PPV23 at 50 and 65 years; (2) annual influenza vaccine and PPV23 at 65 years (similar with the current vaccination programme); (3) PPV23 at 50 and 65 years; (4) PPV23 at 65 years; and (5) no vaccination. We evaluated the incremental cost-effectiveness ratio (ICER) and used Monte Carlo simulation for probabilistic sensitivity analysis. The cost-effectiveness threshold was extracted from previous literature.ResultsIn comparison with no vaccination, all strategies were cost-effective with ICERs less than the threshold (US$24,302 per QALY gained). When compared with no vaccination, strategies 1–4 saved US$ 49.5, US$ 94.9, US$ 584.3, and US$ 1114.2 to gain one QALY respectively. In comparison with strategy 2, strategy 1 spent US$ 195.3 to gain one QALY, whilst strategies 3 and 4 showed less effectiveness with increased costs.ConclusionsAll vaccination strategies were cost-effective, among which the strategy of PPV23 at 50/65 years with annual influenza vaccine was cost-effective even in comparison with current vaccination programme. These findings could help inform the design and implementation of vaccination strategies.     

Therapeutic vaccination with MVA-HIV-1 nef elicits Nef-specific T-helper cell responses in chronically HIV-1 infected individuals

Vaccination is currently considered as an additional therapeutic approach to stimulate HIV-specific immune response in subjects that could not naturally control HIV. Ten chronically HIV infected individuals have been vaccinated with a modified vaccinia Ankara (MVA)-HIV-1(LAI)-nef vector in order to assess safety and immunogenicity. No significant adverse effects were observed during the course of vaccination indicating for the first time that the highly attenuated vaccinia-virus vector MVA is safe in HIV-1 infected individuals. We observed a CD4 T-cell response to Nef in the majority of vaccinated chronically HIV infected individuals. In two subjects CD4 T-cell response was directed to previously unidentified Nef epitopes. The strong Nef-specific CD4 T-cell response elicited by MVA-nef vaccination provides a rationale for immunotherapeutic interventions in HIV infected individuals with suppressed CD4 T-cell responses. Moreover, the CD4 T-cell response elicited was comparable with that usually detected in long-term non-progressor (LTNP) suggesting an improvement in the immunological status of the vaccinated subjects. Furthermore, the new putative CD4 epitopes described here hold promise as important tools for epitope-based vaccination.     

Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in elderly people: a 1-year follow-up

To assess the effectiveness of influenza and pneumococcal vaccination in reducing hospitalisation and deaths in elderly people, the population aged > or =65 years in Stockholm County, Sweden (n = 259627) were invited to take part in a vaccination campaign with influenza and 23-valent pneumococcal vaccine (PV). A no. of persons (100,242) (vaccinated cohort) were vaccinated with one or both vaccines during the campaign. The incidence of hospital admissions during 1 year after the vaccination campaign, adjusted for sex and age, was significantly lower in the vaccinated than in the unvaccinated cohort for influenza (relative risk [RR] 0.68), pneumonia (RR 0.78), and invasive pneumococcal disease (RR 0.46). In the vaccinated cohort, the in-hospital mortality was lower for pneumonia (RR 0.55), COPD (RR 0.53) and cardiac failure (RR 0.72).     

Antibody but not memory B-cell responses are tuned-down in vertically HIV-1 infected children and young individuals being vaccinated yearly against influenza

Yearly immunization against seasonal influenza is highly recommended for HIV-1 infected individuals but evaluating the success of vaccination by serological markers may not be fully informative in this population. Recently, it has been hypothesized that the generation of long-lasting immune responses may depend on whether similar antigens challenge the immune system frequently and intermittently. In the present study, in order to search for additional correlates of vaccine-induced protective immunity and to further dissect this theory, both humoral and memory B-cell responses to the trivalent 2012–2013 seasonal influenza vaccination has been evaluated by strain-specific (separately for H1N1, H3N2 and B strain) standard hemagglutination inhibition (HI) assay and B-cell enzyme-linked immunosorbent spot (ELISpot) in a cohort of vertically HIV-1 infected children and young individuals as compared to age-matched healthy controls. A high number of HIV-1 infected individuals had protective antibody levels prior to vaccination and showed low seroconversion rates after vaccination as compared to healthy controls. On the contrary, similar frequencies of influenza-specific memory B-cells were detected by B-cell ELISpot in both groups suggesting that an adequate B-cell response has been elicited. Data from the H1N1 strain, which is recurrent in seasonal influenza vaccines since 2009, pointed out decreasing antibody but not memory B-cell responses for HIV-1 infected patients being vaccinated for a greater number of years. Further investigations are required to standardize the influenza-specific B-cell ELISpot and to understand whether it could be used routinely as an additional tool to evaluate response to influenza vaccination in immune-compromised individuals being vaccinated yearly.     

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

BackgroundPatients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination.MethodsIn a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination.ResultsPCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS + TNF-α treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response.ConclusionPCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments.The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).     

Interpretability and robustness of sieve analysis models for assessing HIV strain variations in vaccine efficacy

From data on HIV-1 characteristics measured on viruses isolated from vaccinated and unvaccinated persons infected while enrolled in preventive HIV-1 vaccine trials, interpretable inferences into strain variations of vaccine efficacy can be made with recently developed sieve analysis models. Four assumptions are needed for the parameters in these models to have meaningful interpretations in terms of vaccine-induced reductions in strain-specific per-contact transmission probabilities: (A1) vaccination impacts each strain-specific transmission probability homogeneously in vaccinated persons (leaky vaccine effect); (A2) for each strain biological susceptibility to infection given exposure is homogeneous among vaccinated trial participants and among unvaccinated trial participants; (A3) the distribution of exposure is equal in vaccinated and unvaccinated trial participants; (A4) the relative prevalence of circulating HIV-1 strains during the trial follow-up period is constant. Through theoretical considerations and simulations of an ongoing phase III HIV-1 vaccine efficacy trial in Bangkok, we evaluate the importance and necessity of these assumptions. We show that the models still provide estimates of biologically interpretable parameters when A1 is violated, but with bias the extent to which vaccine protection is heterogeneous. We also show that the models are highly robust to departures from A4, with implication that the time-independent models are adequate for applications. In addition, we suggest extensions of the sieve analysis models which incorporate random effects that account for unmeasured heterogeneity in infection risk. With these mixed models, usefully interpretable strain-specific vaccine efficacy parameters can be estimated without requiring A2.The conclusion is that A3, which is justified by randomization and blinding, is the essential assumption for the sieve models to provide reliable interpretable inferences into strain variations in vaccine efficacy.