Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans

Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed. In particular, the antibody response to primary vaccinations and boosters, and the waning of antibody post primary vaccination and post booster were investigated. The significance of gender, age at vaccination, vaccine manufacturer and vaccination intervals were also evaluated. These data confirm that rabies vaccination can elicit a neutralising antibody response that can remain at detectable levels for a number of years, without additional booster vaccinations. The antibody response following both primary vaccination and booster was significantly influenced by the gender of the subject (p = 0.002 and 0.03 respectively), with supportive data that suggests an effect by the make of vaccine administered following primary vaccination, with significantly higher VNA titres observed for one vaccine manufactured prior to 2006 (p < 0.001) in a small subset of recipients (n = 5). Additionally, the decay rate was demonstrated through the overall decline in antibody titre for all individuals, which was a 37% and 27% reduction per 2-fold change in time following primary and booster vaccination respectively. Individuals within older age groups demonstrated a significantly faster decline in antibody titre following the primary vaccination course (p = 0.012). Rate of decline in antibody titre was also significantly influenced by the vaccine make following primary course (p < 0.001). The assessment of neutralising antibody titre decline has also provided an insight into the most appropriate timing for booster administration, and enabled the prediction of long term titres from post-vaccination antibody titres.     

Incidence and variables associated with inadequate antibody titers after pre-exposure rabies vaccination among veterinary medical students

Background

This study sought to determine the proportion of subjects with inadequate antibody titers at two years after pre-exposure rabies vaccination and identify variables associated with inadequate antibody titers.

Methods

A retrospective chart review of vaccination records of veterinary students in Michigan, 2004–2009, was conducted. Antibody titers <0.5 IU/ml as estimated by rapid fluorescent focus inhibition test were classified as inadequate. Variables were compared between the two groups to identify factors associated with inadequate titers at two years.

Results

A total of 603 subjects (mean age 24.1 ± 4.2 years, male:female 106:497) were included. Nearly one third (177/603, 29.4%) had inadequate titers at two years. Male gender (adjusted odds ratio (AOR) 1.87, 1.07–3.27; p = 0.029), vaccine manufacturer (AOR 1.49, 1.16–1.92; p = 0.002), BMI >25 (AOR 1.61, 1.02–2.54; p = 0.043), and duration between first and third doses of vaccine >21 days (AOR 2.49, 1.26–4.97; p = 0.009) were independently associated with inadequate titers.

Conclusions

Twenty-nine percent of subjects had inadequate antibody titers against rabies at 2 years. Gender, vaccine type/manufacturer, BMI of 25 or greater, and more than 21 days between the first and third doses of vaccine were independently associated with inadequate antibody titers at two years. Our data would support modifying the recommendations, so the third dose is recommended at 21 days rather than 21–28 days.     

Rabies vaccination for international travelers

Rabies prevention in travelers is a controversial issue. According to experts, the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveler, the rabies endemicity and access to appropriate medical care in the country of destination. However, no detailed information is available regarding the last two determinants in many regions. Twenty-two cases of rabies were reported in tourists, expatriates and migrant travelers over the last decade, including three cases following short-term travel of no more than two weeks. Studies on rabies post-exposure prophylaxis (PEP) in travelers show that overall, 0.4% (range 0.01-2.3%) of travelers have experienced an at-risk bite per month of stay in a rabies-endemic country, while 31% of expatriates and 12% of tourists were vaccinated against rabies before traveling. The main reason cited by travelers for not being vaccinated is the cost of the vaccine. The majority of patients who sustained a high risk injury was not vaccinated against rabies before traveling and were not properly treated abroad. From available studies, the following risk factors for injuries sustained from potentially rabid animals may be identified: traveling to South-East Asia, India or North Africa, young age, and traveling for tourism. The duration of travel does not appear to be a risk factor. It should be noted that “at-risk activities” have not been addressed in these studies. Detailed rabies distribution maps and information on the availability of rabies biologics are urgently needed in order to identify those travelers who need pre-travel vaccination. Meanwhile, cost-minimization of rabies pre-exposure vaccination may be achieved in several ways, notably by using the intra-dermal method of vaccination.     

One-week intramuscular or intradermal pre-exposure prophylaxis with human diploid cell vaccine or Vero cell rabies vaccine,followed by simulated post-exposure prophylaxis at one year: A phase III,open-label,randomized, controlled trial to assess immunogenicity and safety

Shorter rabies pre-exposure prophylaxis (PrEP) regimens may offer improved convenience and feasibility over classic 3-week regimens, for example in regions with poor access to vaccines or for travelers to rabies-endemic regions. In this multicenter, open-label, controlled trial, 570 healthy participants aged 2–64 years were randomized to receive: 1-week PrEP (vaccination days [D]0 and 7; Group 1) or classic 3-week PrEP regimen (D0, D7, and D21; Group 2) with one 1.0 mL intramuscular [IM] dose of human diploid cell culture rabies vaccine (HDCV) at each visit; 1-week PrEP with two 0.1 mL intradermal (ID) HDCV doses at each visit (Group 3); or 1-week PrEP with one 0.5 mL IM dose (Group 4) or two 0.1 mL ID doses (Group 5) of Vero cell rabies vaccine (PVRV) at each visit. Participants received simulated post-exposure prophylactic (PEP) vaccination (two IM or ID doses of HDCV or PVRV three days apart) one year later. Rabies virus neutralizing antibody titers and seroconversion (titers ≥ 0.5 IU/mL) rates were assessed 14 days and up to 1 year post-PrEP, and pre- and post-PEP. Safety was assessed throughout the study. Seroconversion rates were high 14 days post-last PrEP injection (ranging from 96.7 % to 97.2 % across groups 1, 3–5; 1-week PrEP) and reached 100 % in Group 2 (3-week PrEP). Non-inferiority of Group 1 versus Group 2 in terms of seroconversion rates 14 days post-last PrEP injection (primary objective) was not demonstrated. After simulated PEP, all groups showed rapid and robust immune responses, with all but one participant achieving seroconversion (titers ≥ 0.5 IU/mL). There were no safety concerns, and the tolerability profiles of the vaccines were similar across the groups.A 1-week, IM or ID PrEP regimen with HDCV or PVRV provided efficacious priming, enabling rapid robust anamnestic responses to simulated PEP 1 year later across age groups.ClinicalTrials.gov number: NCT03700242.WHO Universal Trial Number (UTN): U1111-1183-5743.     

中国预防控制狂犬病降低发病率的思考

近年来,中国狂犬病发病数急剧上升,从1996年的159例,上升到2006年的3 000多例。为预防控制狂犬病,降低发病率,以下几项措施应加以考虑:(1)对犬应加强管理和大规模免疫,犬用疫苗应改进。根据世界卫生组织(WHO)狂犬病专家建议,注射用兽用疫苗应为灭活疫苗。国内应尽快生产安全、有效、价廉的灭活疫苗取代现行的兽用减毒活疫苗,产量应提高以满足大规模犬免疫的需求。(2)暴露前免疫应扩大到狂犬病流行区<15岁儿童。(3)暴露后的疫苗接种率应提高,全程免疫的费用应降低,以便大多数居民能用得起现有的细胞培养疫苗,有效的措施是,采用WHO推荐的皮内多点免疫方案,既能节省相当可观的疫苗用量,又可降低疫苗免疫费用。(4)对免疫失败病例应进行调查,特别是对现有各种疫苗生产用的毒株与目前流行的狂犬病野毒株间的基因和抗原特性的研究和比较分析。     

Immunogenicity and safety of two-visit,intradermal pre-exposure rabies prophylaxis simultaneously administrated with chimeric live-attenuated Japanese encephalitis vaccine in children living in rabies and Japanese encephalitis endemic country

BackgroundReducing the number of doses required for pre-exposure prophylaxis (PrEP) would make it more feasible and cost-effective to implement in children at the highest risk of rabies exposure in Asia. We studied immune response of 2-site intradermal (ID) injection of rabies vaccine on days 0 and 28 for rabies PrEP simultaneously administrated with live-attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) for children living in endemic area.Research design and methodsSeronegative children (n = 49) aged 12–16 months were randomized 2:1 into two groups: Group A subjects were vaccinated with 0.1-mL ID injection of purified Vero cell rabies vaccine (PVRV), each at two sites on day (D) 0 and D28; Group B subjects were vaccinated with conventional 0.5-mL intramuscular PVRV on D0, D7 and D28. Both groups received one dose of JE-CV subcutaneously on D0 and D365. Rabies virus neutralizing antibody (RVNA) titers were measured on D0, D42 and D365 after vaccination; Japanese Encephalitis (JE) neutralizing antibody titers were determined on D0, D42, D365 and D379.ResultsAll children had RVNA ≥ 0.5 IU/mL on D42 (geometric mean titers [GMTs] of RVNA 14.35 IU/mL [Group A] and 14.83 IU/mL [Group B], p > 0.05]). On D365, RVNA GMTs of subjects in group A and B were 1.50 IU/mL and 2.00 IU/mL (p > 0.05), respectively. All children had seroprotection following booster dose of JE-CV. There were no vaccine-related SAEs observed.ConclusionThe 2-site ID PrEP with PVRV on days 0 and 28 co-administrated with JE-CV are safe and immunogenic.     

Safety and immunogenicity of a serum-free purified Vero rabies vaccine in healthy adults: A randomised phase II pre-exposure prophylaxis study

A serum-free, highly purified Vero cell rabies vaccine (PVRV-NG) is under development. We previously demonstrated that pre-exposure prophylaxis (PrEP) with PVRV-NG had a satisfactory safety profile and was immunogenically non-inferior to the licensed purified Vero cell rabies vaccine in adults. Here, we evaluated the safety and immunogenic non-inferiority of PrEP with PVRV-NG compared to the licensed human diploid cell vaccine (HDCV) in healthy adults (NCT01784874). Participants received three vaccinations (days 0, 7, and 28) as PrEP with or without a booster injection after 12 months. Rabies virus neutralising antibodies (RVNA) were evaluated on days 0, 28 (subgroup only), and 42, and Months 6, 12, and 12 + 14 days (booster group only). Non-inferiority (first primary objective) was based on the proportion of participants with RVNA titres ≥ 0.5 IU/mL (World Health Organization criteria for seroconversion) on day 42, expected to be ≥ 99% (second primary objective). Safety was evaluated after each dose and monitored throughout the study. At day 42, PVRV-NG was non-inferior to HDCV and the first primary objective was met; seroconversion was observed for 98.3% of PVRV-NG recipients and 99.1% of HDCV recipients. As < 99% of participants in the PVRV-NG group had RVNA titres ≥ 0.5 IU/mL, the second primary objective was not met. Booster vaccination produced a strong increase in RVNA titres for all groups, primed with PVRV-NG or HDCV. RVNA geometric mean titres tended to be higher for HDCV than PVRV-NG primary vaccine recipients. In a complementary evaluation using alternative criteria for seroconversion (complete virus neutralization at 1:5 serum dilution), 99.6% and 100% of participants in the PVRV-NG and HDCV groups, respectively, achieved seroconversion across the vaccine groups. No major safety concerns were observed during the study. PVRV-NG was well tolerated, with a similar safety profile to HDCV in terms of incidence, duration, and severity of adverse events after primary and booster vaccinations.ClinicalTrials.gov number: NCT01784874.     

A serum-free,purified vero cell rabies vaccine is safe and as immunogenic as the reference vaccine Verorab™ for pre-exposure use in healthy adults: Results from a randomized controlled phase-II trial

Background

Verorab™ was licensed in 1985 for both pre- and post-exposure prophylaxis of rabies. The next generation purified Vero cell rabies vaccine (PVRV-NG) is a highly purified vaccine. We performed a phase II clinical study in adults in France to assess its immunological non-inferiority and clinical safety for pre-exposure prophylaxis.

Methods

In a randomized phase-II trial, 384 healthy adult subjects were randomized (2:1) to receive a three-dose primary series of PVRV-NG or Verorab. One year later, the PVRV-NG group received a PVRV-NG booster while the Verorab group participants were randomized to receive a booster of PVRV-NG or Verorab for. Rabies virus neutralizing antibodies (RVNA) were evaluated on days 0, 28 (subgroup), 42, months 6, 12 and 12 + 14 days. Safety was evaluated for seven days after each dose. Adverse event between doses, until 28 days after the final dose was recorded. Serious adverse events were recorded up to 6 months after the last dose.

Results

The criterion for non-inferiority was met in the per-protocol analysis set and confirmed in the full analysis set (FAS). In the FAS, 99.6% and 100% of subjects had RVNA titers ≥0.5 IU/mL in PVRV-NG and Verorab groups, respectively. While RVNA levels gradually decreased over the 12-month period, at 6 and 12 months after vaccination >89% and >77%, respectively, in both groups had RVNA titers ≥0.5 IU/mL. The PVRV-NG booster induced a strong response, irrespective of the vaccine given for the primary series. PVRV-NG was safe and well tolerated and its safety profile was similar to Verorab for unsolicited adverse events and solicited systemic reactions. The incidence of solicited injection-site reactions was lower with PVRV-NG than with Verorab after the primary series and the booster dose.

Conclusions

PVRV-NG was shown to be at least as immunogenic as Verorab and to present a similar safety profile.     

MSM人群对HIV暴露前预防知识知晓及相关因素研究

目的  了解不同城市和年份的男男性行为者(men who have sex with men, MSM)对HIV暴露前预防(pre-exposure prophylaxis, PrEP)知识知晓变化情况及其影响因素。方法  依托社区组织分别在2019年和2021年采用电子问卷收集北京市、深圳市和昆明市的MSM人群的基本社会人口学情况、PrEP知识知晓、行为学情况等,并进行相关因素分析。结果  共调查4 889名MSM,其中2019年2 399人,2021年2 490人。2019年PrEP知识知晓占6.29%,2021年占25.02%。多因素logistic回归分析模型分析结果显示,2019年调查对象PrEP知识知晓促进因素包括年龄在25~ < 35岁(OR=1.685, 95% CI: 1.007~2.821)和≥35岁(OR=29.01, 95% CI: 1.156~3.497)、咨询过PrEP(OR=1.731, 95% CI: 1.050~2.855)、暴露后预防(post-exposure prophylaxis, PEP)知识知晓(OR=3.178, 95% CI: 2.079~4.860)。2021年调查对象PrEP知识知晓相关因素包括文化程度(本科/大专：OR=3.291, 95% CI: 1.595~6.793;研究生及以上：OR=4.507, 95% CI: 2.104~9.652)、曾咨询过PrEP(OR=2.591, 95% CI: 1.906~3.521)、PEP知识知晓(OR=5.855, 95% CI: 3.071~11.161)、使用过PEP(OR=1.619, 95% CI: 1.191~2.200)、使用助性剂(OR=0.623, 95% CI: 0.492~0.789)、一年内检测次数为3~4次(OR=2.140, 95% CI: 1.265~3.619)和≥5次(OR=3.414, 95% CI: 1.987~5.865)。结论  2021年MSM的PrEP知识知晓水平较2019年大幅度提高,但总体仍然低。影响知晓水平的相关因素包括MSM年龄、文化程度、进行过HIV检测、知晓及应用过PEP措施等,应继续采取综合性的措施加强对MSM人群关于PrEP的宣传教育,提高其对PrEP正确的认知。     

A randomized open-label trial of 2-dose or 3-dose pre-exposure rabies prophylaxis among Thai children

BackgroundWorld Health Organization changed the recommendation for pre-exposure rabies prophylaxis from 3-dose to 2-dose regimen in 2018. Given limited data of 2-dose regimens in pediatric population, this study aimed to compare the immunogenicity between 2-dose and 3-dose pre-exposure rabies immunization.MethodsThis study was conducted among healthy children aged 2–12 years. They were randomized to 2-dose vaccination (2D) on days 0 and 28 or 3-dose vaccination (3D) on days 0, 7, and 28. Purified Vero cell rabies vaccine (PVRV-Verorab™) was administered intramuscularly. Rabies virus neutralizing antibody (RVNA) titers were measured at 3 time points: 14-day after complete vaccination, 1-year pre-booster vaccination, and 7-day post-booster dose to mimic scenario of rabies exposure. RVNA titers ≥0.5 IU/ml were considered adequate antibody. T cell specific response to rabies vaccine antigen was measured using the interferon-gamma enzyme linked immunospot assay.ResultsFrom September to October 2017, 107 participants (51% males), 78 in 2D group and 29 in 3D group were enrolled. Median age was 5.8 years (IQR 4.4–7.3). All participants had RVNA titers ≥0.5 IU/ml after primary vaccination [GMT 2D: 18.6 (95%CI 15.9–21.8) and 3D: 16.3 (95%CI 13.2–20.1 IU/ml), p = 0.35]. At 1-year prior to receiving the booster, only 80% of the children in 2D group maintained RVNA titers ≥0.5 IU/ml compared to 100% of the children in 3D group (p = 0.01). However, all participants in both groups had RVNA ≥0.5 IU/ml at 7-day post booster vaccination [GMT 2D: 20.9 (95%CI 17.4–25.3) and 3D: 22.2 (95%CI 15.8–31.4) IU/ml (P = 0.75)]. The median number of IFN-γ secreting cells at 7-day post-booster dose was 98 and 128 SFCs per 10⁶ PBMCs in the 2D and 3D groups, respectively (P = 0.30).ConclusionsTwo-dose primary rabies immunization provided adequate antibody at post primary vaccination and post booster. The results support 2-dose regimen of pre-exposure rabies immunization in the pediatric population.     

山东省男男性行为人群HIV暴露前后预防用药情况及相关因素分析

目的 了解山东省MSM的HIV暴露前后预防（PrEP/PEP）用药情况并分析相关因素,为PrEP/PEP工作的推广提供参考依据。方法 2022年4-7月在山东省7个城市监测哨点招募MSM进行问卷调查,每个城市样本量为400人。收集MSM社会人口学、性行为、PrEP/PEP用药等信息,并采集血标本做HIV和梅毒抗体检测。结果 研究对象MSM共2 815人,以≤30岁（55.7%,1 569/2 815）、未婚（68.6%,1 931/2 815）、大专及以上文化程度（56.5%,1 590/2 815）为主。PrEP用药者占9.2%（258/2 815）;PEP用药者占10.8%（305/2 815）。多因素logistic回归分析结果显示,MSM中PrEP用药的可能性较高的相关因素包括年龄≤30岁（aOR=4.04,95%CI：1.25~13.01）、自我认知HIV感染风险较低（aOR=1.76,95%CI：1.16~2.68）、最近6个月发生群交行为（aOR=1.51,95%CI：1.10~2.09）、最近6个月发生同性商业性行为（aOR=1.69,95%CI：1.16~2.47）、使用新型毒品（aOR=1.53,95%CI：1.11~2.11）、接受同伴教育（aOR=1.56,95%CI：1.03~2.37）、知晓别人PrEP用药（aOR=3.29,95%CI：2.48~4.36）、HIV抗体阴性（aOR=8.40,95%CI：1.12~63.12）;MSM中PrEP用药的可能性较低的相关因素为主要性伴为临时性伴（aOR=0.67,95%CI：0.49~0.90）。MSM中PEP用药的可能性较高的相关因素包括年龄<50岁（≤30岁：aOR=2.41,95%CI：1.02~5.69;31~49岁：aOR=3.33,95%CI：1.42~7.85）、自我认知无HIV感染风险（aOR=1.87,95%CI：1.12~3.11）、最近6个月发生群交行为（aOR=1.68,95%CI：1.23~2.29）、使用新型毒品（aOR=3.86,95%CI：2.94~5.07）以及未接受同伴教育（aOR=1.54,95%CI：1.12~2.12）。结论 山东省MSM的PrEP/PEP用药比例较高。应加强同伴教育和自我认知HIV风险教育,提高MSM中PrEP/PEP用药的使用率。     

Neutralizing antibody response after intradermal rabies vaccination in hemodialysis patients

Abnormal immune function in chronic hemodialysis (HD) patients could impair immunologic responsiveness to various vaccinations. Such inadequate response makes the HD patients to be at risk of certain fatal but preventable diseases including rabies. Although the effectiveness of rabies vaccination has been established in healthy subjects, the responsiveness of the current rabies vaccination has never been examined in HD patients. The effectiveness of post-exposure rabies vaccine was assessed in 20 stable thrice-a-week chronic HD patients who received adequate dialysis and did not have history of rabies vaccination during the last 20 years. All participants received the standard intradermal Thai Red Cross post-exposure rabies vaccination. Blood samples were obtained for determination of rabies neutralizing antibody (Nab) before the first dose (day 0) and on days 14 and 90 after vaccination. Prior to simulated vaccination, six of twenty patients already had Nab titers above the protective levels of 0.5 IU/mL while the remaining fourteen patients showed undetectable Nab. All subjects reached Nab titers above 0.5 IU/mL(acceptable level for rabies protection) by days 14 after vaccination. The geometric mean titers (GMTs) on days 14 after vaccination were 3.2 + 3.1 IU/mL (range 0.81–9.17 IU/mL). At day 90 after vaccination, 13 of 14 patients had Nab titers above the protective levels, resulting in the response rate of 92.8%. The GMTs of Nab on day 90 after vaccination were 5.09 + 1.79 IU/mL (0.42–25.0 IU/mL). There were no correlations between Nab titers and patient characteristics. No serious adverse reactions were detected. In conclusion, chronic HD patients receiving adequate dialysis have excellent protective immunological response after intradermal post-exposure rabies vaccination as WHO recommendation.     

广西女性性工作者暴露前药物预防HIV感染接受意愿及其影响因素研究

目的 了解广西地区南宁、柳州、北海市女性性工作者(FSWs)对暴露前药物预防(PrEP)HIV感染的接受意愿及其影响因素.方法 采用横断面设计,方便抽样的方法选取3市405名FSWs进行问卷调查,了解FSWs的AIDS相关危险行为、对PrEP的知晓情况及其接受意愿.结果 在了解PrEP后,对于“如果PrEP预防HIV感染安全、有效且免费提供”,405人中有85.9％表示愿意接受.logistic回归分析显示,与PrEP接受意愿有关的因素为:工作场所(OR=2.256,P=0.009)、月经济收入(OR=0.257,P=0.004)、与家人的关系(OR=0.338,P=0.012)、AIDS知晓情况(OR=2.802,P=0.028)、认为HIV感染危险来自陌生性伴(OR=0.363,P=0.049)、老板是否规定使用安全套(OR=0.432,P=0.01 0)、商业性行为时是否全程使用安全套(OR=3.010,P=0.002)、是否使用过药物预防性病(OR＝3.570,P=0.049).结论 对HIV/AIDS相关知识的知晓程度及自我保护意识的高低可能是影响FSWs接受PrEP的主要因素.以健康教育的形式宣传PrEP是提高其接受意愿的较好方式.     

Evidence for a 4-dose vaccine schedule for human rabies post-exposure prophylaxis in previously non-vaccinated individuals

After exposure, human rabies is preventable by prompt application of post-exposure prophylaxis. Historically, the total number of rabies vaccine doses administered during human prophylaxis has decreased, as modern biologics have improved and scientific knowledge has grown. A review of the literature on rabies virus pathogenesis, experimental animal studies, clinical trials, epidemiological surveillance, and economic analyses was conducted to determine the potential utility of reducing the current 5-dose intramuscular series of human rabies vaccine administered in the United States. Based upon the available evidence, a reduced schedule of cell-culture rabies vaccine, administered on days 0, 3, 7, and 14, given in conjunction with rabies immune globulin, was supported and recommended by the United States Advisory Committee on Immunization Practices.     

男男性行为人群HIV暴露前预防需求与使用障碍研究

目的 了解MSM对HIV暴露前预防（PrEP）的实际需求及阻碍其使用的相关因素。方法 通过同性社交Blued 6.5.0软件、MSM同伴推荐等方法招募MSM为调查对象，估算样本量600人。利用"问卷星"平台，在调查员的指导下进行匿名电子问卷调查，调查内容包括一般情况、PrEP相关知识和使用意愿与顾虑、PrEP实际需求及PrEP使用自我效能等。结果 共调查622名MSM，知晓和曾使用过PrEP的比例分别为56.4%（351/622）和4.3%（27/622）；67.2%（418/622）有PrEP实际需求，PrEP使用自我效能良好的为21.2%（132/622）。结构方程模型分析结果显示，PrEP相关知识和使用顾虑对PrEP使用自我效能发挥直接正向作用，效应系数分别为0.08和0.13，自我歧视是由于PrEP使用顾虑而间接影响PrEP使用自我效能，效应系数为0.035；广义线性混合模型分析结果表明，曾使用过PrEP可增加使用自我效能（OR=5.55）；PrEP相关知识和使用顾虑每增加1分，PrEP使用自我效能分别增加0.14倍和0.07倍。担心药物副作用、预防效果和费用者分别占61.1%（380/622）、60.1%（374/622）和53.2%（331/622）；期望获取PrEP服务途径主要为CDC（75.6%，470/622）、MSM社会组织（65.4%，407/622）和互联网（63.8%，397/622）。结论 MSM对PrEP呈现高需求与低使用的较大差距，PrEP相关知识缺乏、自我歧视、对药物预防效果、副作用及费用的顾虑是阻碍MSM使用PrEP的因素，故需要建立适合MSM特点的PrEP服务模式，以满足MSM对PrEP干预的需求。     

北京市男男性行为者HIV新发感染率与高危行为及接受暴露前后预防用药服务情况调查

目的 了解北京市MSM的HIV新发感染率与高危行为及接受暴露前后预防（PrEP/PEP）用药服务情况。方法 采用Epi Info7.0软件计算参加横断面调查和队列调查样本量分别为1 227人和207人年。采用方便抽样法通过手机微信公众号招募MSM参加自填式网络问卷调查,收集其社会人口学、高危行为及接受PrEP/PEP用药服务利用情况,MSM自行采集干血斑样本邮寄到指定实验室进行HIV核酸检测。建立HIV核酸阴性受检者开放式队列,随访观察至研究终点。采用非条件logistic回归分析MSM最近1个月无保护肛交行为、最近1个月同性多性伴的影响因素。结果 共招募MSM 1 147人,其中HIV核酸阴性者956人观察236人年。HIV新发感染率为1.3/100人年（3/236）。最近1个月肛交和口交每次都使用安全套者分别占50.7%（238/469）和4.9%（23/469）。最近1个月与HIV感染者发生性行为的比例为5.9%（43/723）。分别有9.8%（103/1 049）和8.7%（91/1 049）的研究对象曾接受PrEP/PEP用药服务。PrEP/PEP用药期间发生性行为每次使用安全套的比例分别为34.3%（24/70）和72.2%（39/54）。多因素logistic回归分析结果显示,接受PrEP/PEP用药服务者的最近1个月发生无保护肛交行为和有同性多性伴的可能性均较高（aOR=3.16,95%CI：1.45~7.18;aOR=2.64,95%CI：1.19~6.30）;最近1个月使用毒品或Rush Popper者的最近1个月发生无保护肛交行为和有同性多性伴的可能性均较高（aOR=2.34,95%CI：1.67~3.30;aOR=2.42,95%CI：1.76~3.33）。结论 应在MSM中倡导坚持使用安全套及开展常见滥用药物危害的健康教育。在PrEP/PEP用药服务咨询中,需提示MSM坚持使用安全套的重要性。     

Serum-free purified Vero rabies vaccine is safe and immunogenic in children: Results of a randomized phase II pre-exposure prophylaxis regimen study

BackgroundA serum-free, highly purified Vero rabies vaccine (PVRV-NG) has been developed with no animal or human components and low residual DNA content. A phase II randomized clinical study aimed to demonstrate the non-inferiority of the immune response and assess the safety profile of PVRV-NG versus a licensed human diploid cell culture rabies vaccine (HDCV) in a pre-exposure regimen in healthy children and adolescents in the Philippines.MethodologyChildren aged 2–11 years and adolescents aged 12–17 years were randomized (2:1) to receive three injections of either PVRV-NG or HDCV (on day [D] 0, D7 and D28). Rabies virus-neutralizing antibodies (RVNA) were measured at D0, D42 and 6 months after the first injection (month [M] 6). Safety was assessed during the vaccination period and up to 28 days after the last vaccination. Serious adverse events were followed until 6 months after last vaccination.Principal findings342 healthy participants (171 children and 171 adolescents) were randomized and followed for 6 months after the last dose. All participants in both groups had an RVNA titer ≥ 0.5 IU/ml at D42, demonstrating non-inferiority in seroconversion rate for PVRV-NG versus HDCV. Over 90% of participants had RVNA titer ≥ 0.5 IU/ml at M6. PVRV-NG was well tolerated after each vaccination and up to 6 months following the last dose. There were no major safety concerns during the study, and the type and severity of solicited adverse events was similar for both treatment groups.ConclusionsThis study demonstrated the non-inferior immune profile of PVRV-NG compared with HDCV in a pre-exposure setting within a pediatric population. PVRV-NG was well tolerated with no safety concerns. This study is registered at ClinicalTrials.gov (NCT01930357) and EU Clinical Trials Register (2015–003203-30).     

成都市男男性行为人群艾滋病暴露前预防用药服药依从性分析

目的 了解成都市MSM人群在艾滋病暴露前预防用药（PrEP）的依从性及影响因素。方法 按照随机、开放、多中心平行对照临床干预研究,于2013年7月1日至2015年9月30日按照样本量估算,采用滚雪球法招募合格的研究对象为HIV高感染风险且HIV检测结果阴性的MSM,共328人,随机化分配为每日用药组、高危行为前后用药组和空白对照组,每 3个月进行临床随访和问卷调查。评价每日用药组、高危行为前后用药组的服药依从性,并用logistic回归模型探讨PrEP服药依从性的影响因素。结果 共分析141名研究对象,41.8%（59/141）PrEP服药依从性好,每日用药组和高危行为前后服药组的PrEP服药依从性分别为69.0%（49/71）、14.3%（10/70）,差异有统计学意义（χ²=45.29,P<0.001）。多因素logistic分析结果显示,用药方式是PrEP服药依从性的影响因素,相比于每日用药组,高危行为前后用药组的服药依从性相较差（OR=0.07,95%CI：0.03~0.16）。结论 MSM人群PrEP服药依从性总体不够理想,用药方式是PrEP服药依从性的主要影响因素。     

暗娼对HIV暴露前预防药物的认知及使用意愿研究进展

暗娼在性行为过程中处于弱势地位,HIV感染风险较高。在暗娼中推广暴露前预防（PrEP）药物可以预防感染HIV。本文综述了暗娼对PrEP药物的认知情况、使用意愿、影响因素和潜在风险补偿,为扩大PrEP药物在该人群中的运用提供参考依据。     

Rabies post-exposure vaccination in 2 visits within a week: A 4-site intradermal regimen

Rabies is fatal in all unvaccinated patients bitten by dogs, and so post-exposure vaccine regimens must be robust enough to ensure their survival under all conditions. Treatment tends to be excessive for most people, but there is justified anxiety about reducing vaccine dosage and shortening regimens. Recently, World Health Organisation (WHO) recommended one week primary post-exposure intradermal regimens requiring 3 clinic visits, but these are unlikely to prove economical where rabies vaccination is most needed, in deprived rural areas of Africa and Asia.A highly immunogenic regimen involving two doses of intradermal vaccine given one week apart has advantages over other regimens. Anyone exposed to a possibly rabid animal would be given intradermal (ID) injections at 4 sites using a whole vial of vaccine. Those who had not been previously vaccinated would be given 2-site ID injections using half a vial one week later. Those who might be immunosuppressed could be given an optional single ID dose on day 28. The rationale for this regimen is discussed in the context of the recently revised WHO recommendations for rabies prophylaxis.