Targeting of rotavirus VP6 to DEC-205 induces protection against the infection in mice

Rotavirus (RV) is the primary etiologic agent of severe gastroenteritis in human infants. Although two attenuated RV-based vaccines have been licensed to be applied worldwide, they are not so effective in low-income countries, and the induced protection mechanisms have not been clearly established. Thus, it is important to develop new generation vaccines that induce long lasting heterotypic immunity. VP6 constitutes the middle layer protein of the RV virion. It is the most conserved protein and it is the target of protective T-cells; therefore, it is a potential candidate antigen for a new generation vaccine against the RV infection. We determined whether targeting the DEC-205 present in dendritic cells (DCs) with RV VP6 could induce protection at the intestinal level. VP6 was cross-linked to a monoclonal antibody (mAb) against murine DEC-205 (αDEC-205:VP6), and BALB/c mice were inoculated subcutaneously (s.c.) twice with the conjugated containing 1.5 μg of VP6 in the presence of polyinosinic–polycytidylic acid (Poly I:C) as adjuvant. As controls and following the same protocol, mice were immunized with ovalbumin (OVA) cross-linked to the mAb anti-DEC-205 (αDEC-205:OVA), VP6 cross-linked to a control isotype mAb (Isotype:VP6), 3 μg of VP6 alone, Poly I:C or PBS. Two weeks after the last inoculation, mice were orally challenged with a murine RV. Mice immunized with α-DEC-205:VP6 and VP6 alone presented similar levels of serum Abs to VP6 previous to the virus challenge. However, after the virus challenge, only α-DEC-205:VP6 induced up to a 45% IgA-independent protection. Memory T-helper (Th) cells from the spleen and the mesenteric lymph node (MLN) showed a Th1-type response upon antigen stimulation in vitro. These results show that when VP6 is administered parenterally targeting DEC-205, it can induce protection at the intestinal level at a very low dose, and this protection may be Th1-type cell dependent.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

广西壮族自治区柳州市2013-2014年HIV/AIDS抗病毒治疗后BMI变化及相关因素分析

目的 了解广西壮族自治区柳州市艾滋病病毒感染者/艾滋病患者（HIV/AIDS）抗病毒治疗后BMI变化的动态趋势及相关因素。方法 选择2013年1月1日至2014年12月31日柳州市开始抗病毒治疗、年龄≥ 15岁、治疗基线、第（6±2）个月和（12±2）个月BMI值均有体重记录的HIV/AIDS作为研究对象,收集研究对象体重、身高数据计算BMI。采用PASW Statistics 18.0.0软件进行统计学分析,采用一般线性模型重复测量方差分析方法,进行BMI随时间变化趋势分析和多因素分析。结果 2 871例研究对象治疗基线、第（6±2）个月和（12±2）个月BMI值分别为（20.65±3.32）、（20.87±3.22）和（21.18±3.20）,3个时段的BMI值差异有统计学意义（F=18.86,P<0.001）。治疗后BMI随时间推移而提升（F=37.25,P<0.001）,相关因素主要为年龄、性别、婚姻状态、基线CD₄⁺T淋巴细胞计数和WHO临床分期。结论 柳州市HIV/AIDS抗病毒治疗前BMI诊断营养不良所占的比例较高,接受抗病毒治疗后BMI的变化受多种因素影响,针对不同患者采用不同的治疗措施,有利于患者身体营养状况的恢复。     

当前农村健康教育的现状与对策

农村健康教育亦称农村卫生教育或农村卫生宣传教育,它是我国新农村建设的重要内容之一。重视和加强农村健康教育工作,对促进社会进步有着重要意义。该文对当前农村健康教育的现状问题和对策作一综诛．     

广西部分地区老年男性嫖客商业性行为特征及HIV感染相关危险因素研究

目的 了解广西部分地区老年男性嫖客商业性行为的基本情况和特点,初步探索其感染HIV的相关危险因素.方法 选择广西老年男性艾滋病流行地区,在暗娼场所现场对≥60岁的嫖客开展调查,采5 ml静脉全血样本检测HIV和梅毒抗体,用logistic多因素分析相关危险因素.结果 调查共获得有效问卷1 236份,65.61％来自低档场所,53.64％的人商业性行为中从未使用安全套,47.33％的人商业性行为暴露时间≥10年,53.32％的人近30 d内商业性行为＞2次,检出HIV抗体阳性的嫖客30人(2.43％),梅毒阳性40人(3.24％);有固定性伴(OR=0.302,95％CI:0.140～ 0.650)是老年嫖客感染HIV的保护因素,商业性行为暴露时间(1～5)年(OR=2.552,95％CI:1.086～ 5.998)和近30天内发生商业性行为次数≥4次(OR=3.002,95％CI:1.047～8.607)是危险因素.结论 广西老年男性嫖客HIV、梅毒的感染率较高,以低档场所来源和低档消费为主,商业性行为有暴露起点早,时间跨度长、密度高、缺乏防护等特征,感染HIV的相关危险因素可能包括无固定性伴及频繁发生的商业性行为.     

广西壮族自治区专项示范区HIV筛查项目成本效果分析

目的 对2013年广西壮族自治区3个国家科技重大专项示范县开展的HIV筛查项目进行成本效果分析.方法 计算广西HIV筛查项目实施期间执行的经费,统计项目检出的HIV/AIDS和抗病毒治疗数据,建立马尔科夫(Markov)5树模型,评估该项目获得的质量调整生命年(QALY),分析该项目的成本效果.结果 2013年度广西3个示范县区共投入经费1 920.5万元用于HIV筛查项目,检出HIV/AIDS阳性1 218例,3个示范县HIV/AIDS阳性检出的平均成本为1.456万元/例、1.842万元/例和1.404万元/例,通过检出HIV/AIDS获得的QALY平均数分别为12.736、8.523和8.321个,挽回的QALY总数分别为5 973.184个、3 613.752个和2 704.325个;项目整体成本效果为0.156万元/QALY,各示范县分别为0.114万元/QALY、0.216万元/QALY和0.169万元/QALY,A县成本效果指标优于B、C县.结论 广西示范县HIV筛查项目成本效益较好,但HIV/AIDS阳性检出的平均成本较高,加强HIV/AIDS的抗病毒治疗工作有利于提高该项目的成本效益.     

HIV阳性母亲接受预防艾滋病母婴传播对其所生18月龄儿童体格发育的影响

目的 探讨广西壮族自治区（广西）HIV阳性母亲接受预防艾滋病母婴传播（PMTCT）后对18月龄儿童体格发育的影响,为改进PMTCT方案提供科学依据。方法 选取广西艾滋病疫情位居前3位的钦州市灵山县、柳州市鹿寨县、南宁市横县作为研究现场,按照回顾性病例对照研究设计分为病例组和对照组,病例组研究对象为实施了PMTCT的每年新报告HIV阳性母亲及其所生HIV阴性儿童,来源于全国PMTCT管理信息系统数据库的2010年1月1日至2017年12月31日HIV阳性母亲历史卡片以及其所生HIV阴性儿童,共554例;对照组研究对象为2017年健康母亲及其所生的健康儿童,共1 109例。收集PMTCT相关资料及其18月龄儿童的身高、体重和头围等体格发育资料。儿童体格发育不良的定义为身高、体重和头围的3项主要指标中至少1项指标低于正常值范围。结果 病例组的HIV阳性母亲及其所生儿童分别为667例和554例,其PMTCT率分别为91.15%（608/667）和96.57%（535/554）,儿童的HIV阳性率、死亡率和HIV母婴传播率分别为1.44%（8/554）、3.07%（17/554）和1.91%（8/418）;18月龄儿童健康体检结果显示,体格发育不良者占30.51%（169/554）;对照组儿童1 109例,体格发育不良者占9.83%（109/1 109）,病例组与对照组的体格发育不良率差异有统计学意义（P<0.01）。结论 HIV阳性母亲及其所生儿童的PMTCT率均超过90.00%,但是18月龄儿童的体格发育不良者超过30.00%。PMTCT政策对HIV阳性母亲所生儿童的体格发育不良的可能影响,需做进一步研究。     

Risk of intussusception following rotavirus vaccination: An evidence based meta-analysis of cohort and case-control studies

BackgroundInternational post-licensure studies on rotavirus vaccines have identified an increased risk of intussusception in infants after administration. The first developed rotavirus vaccine (Rotashield (RRV-TV)) was suspended post-licensure in 1999 after an association with intussusception was found. The currently available second-generation rotavirus vaccines (Rotateq (RV5) and Rotarix (RV1)), are recommended as a routine vaccine by the World Health Organisation (WHO). Post-licensure studies of these vaccines have shown a smaller but temporal increased risk for developing intussusception.MethodsA meta-analysis was performed to summarise available evidence and to give an overall risk of developing intussusception from case-control and cohort studies for all rotavirus vaccines that have been manufactured up to date. A search was conducted on MEDLINE, PubMed, EMBASE and Google Scholar up to May 2017. Eligible studies assessed the relationship between the rotavirus vaccine administration and subsequent development of intussusception both after receiving the first dose and after receiving all doses combined. Data was extracted on study characteristics, methods and outcomes. Results were pooled using the random-effect model.ResultsSix cohort studies involving 4506265 total first doses and five case-control studies involving a total sample of 9643 children were included in this analysis. The cohort data revealed that there was an associated increased risk of intussusception after the first 7 days post first dose of the vaccine (RR:3.71, 95% CI:1.08–12.69) and after receiving all doses of the rotavirus vaccine (RR:3.47, 95% CI:1.23–9.78). Similarly, the case-control data found an increased risk of intussusception following the first dose (OR: 8.45, 95% CI: 4.08–17.50) and following all doses (OR: 1.59, 95% CI: 1.11–2.27).ConclusionsFindings of this meta-analysis suggest that the rotavirus vaccine is associated with an increased risk on the development of intussusception, principally seen after administration of the first dose of vaccine.     

Update on the epidemiology of rotavirus in the Middle East and North Africa

Rotavirus (RV) is the leading cause of severe acute gastroenteritis (AGE) worldwide. Consequently, we conducted a systematic literature review on articles studying RV in the 25 countries of the MENA region during the past 15 years (2000–2015). The methods and reporting were set according to the 2015 preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) and based on the elements from the international prospective register of systematic reviews (PROSPERO). Our literature search identified 169 studies meeting our predefined inclusion criteria. Studies reporting on RV were conducted in 19 out of the 24 countries of the MENA region. The largest number of studies was reported in Turkey (n = 32), Iran (n = 31), Saudi Arabia (n = 19) and Egypt (n = 17). The majority of studies reporting on RV gastroenteritis rates were clinical observational studies. In 115 studies out of 169, RV was reported among in-patients whereas 35 studies reported RV among outpatients. The predominantly reported RV genotype in the region was G1[P8] followed by G2[P4] and G9[P8]. The majority of studies (n = 108) were conducted among children less than 5 years of age whereas the remaining studies reported on AGE among other age groups and rarely adults. In MENA countries, RV infection was reported all year round with peaks described in cold as well as hot months. This systematic review provides a current update on the epidemiology of RV-associated gastroenteritis in countries of the MENA region and draws attention to the major gaps existing in the continuous monitoring of RV.     

Stability of heat stable,live attenuated Rotavirus vaccine (ROTASIIL®)

Vaccines currently available across the globe are stored and transported in a continuous cold-chain at 2–8 °C or below −20 °C. A temperature excursion outside this range affects the potency of the vaccines. Such vaccines need to be discarded leading wastage. The Rotavirus disease burden is predominantly reported in developing and low-income countries and therefore, has entered or poised to enter their national immunization programs. These countries already have several limitations for effective storage, maintenance and distribution of vaccines in a cold-chain and this introduction is expected to further stress this fragile ecosystem. To help mitigate the cold chain related issues, SIIPL has developed a thermostable rotavirus vaccine ROTASIIL® which can be stored at a temperature below 25 °C for 36 months, completely by-passing the standard 2–8 °C cold storages. In addition it has the capability to withstand temperatures of 37 °C and 40 °C for 18 months and short term exposure to 55 °C. It can also tolerate a temperature shock of being thawed from an extreme cold temperature of −20 °C to a high temperature of 42 °C. The vaccine contains serotypes G1, G2, G3, G4 and G9 (UK-Bovine reassortant strains procured from National Institute of Health-USA). The vaccine is recently licensed in India.