Construction and evaluation of Bordetella pertussis live attenuated vaccine strain BPZE1 producing Fim3

Pertussis or whooping cough is currently the most prevalent vaccine-preventable childhood disease despite >85% global vaccination coverage. In recent years incidence has greatly increased in several high-income countries that have switched from the first-generation, whole-cell vaccine to the newer acellular vaccines, calling for improved vaccination strategies with better vaccines. We have developed a live attenuated pertussis vaccine candidate, called BPZE1, which is currently in clinical development. Unlike other pertussis vaccines, BPZE1 has been shown to provide strong protection against infection by the causative agent of pertussis, Bordetella pertussis, in non-human primates. BPZE1 is a derivative of the B. pertussis strain Tohama I, which produces serotype 2 (Fim2) but not serotype 3 fimbriae (Fim3). As immune responses to fimbriae are likely to contribute to protection, we constructed a BPZE1 derivative, called BPZE1f3, that produces both serotypes of fimbriae. Whereas nasal vaccination of mice with BPZE1 induced antibodies to Fim2 but not to Fim3, vaccination with BPZE1f3 elicited antibodies to both Fim2 and Fim3 at approximately the same level. In mice, both BPZE1 and BPZE1f3 provided equal levels of protection against clinical isolates that either produce Fim2 alone, both Fim2 and Fim3, or no fimbriae. However, vaccination with BPZE1f3 provided significantly stronger protection against Fim3-only producing B. pertussis than vaccination with BPZE1, indicating that immune responses to fimbriae contribute to serotype-specific protection against B. pertussis infection.     

Reintroducing OPV in Israel on the journey to global polio eradication – Estimation at a low rate of contraindicated population

IntroductionThe 2013 reemergence of wild poliovirus in Israel led to the reinstatement of a routine OPV vaccination. Fearing VAPP in immunocompromised, the MOH regulated contraindications for vaccination candidates and household contacts. In this study we estimate the size of the contraindicated population to OPV vaccination.MethodWe studied vaccination candidates aged 2–9 and 14–23 months and probable household contacts. Using the rate of contraindications extracted for each study group from a medical records database, a statistical model was built to estimate the probability of contraindications in candidates.Results3.9% of the 2–9-month-old study group and 4% of the 14–23-month-old group had contraindications by either self or household contacts.ConclusionA statistical model can provide an estimation of the contraindicated population and can be used in the future when devising vaccination campaigns. In contrast to concerns raised by the MOH, our findings show a smaller than anticipated contraindicated population.     

妇肤康喷雾剂联合乳杆菌活菌胶囊治疗产后阴道炎的疗效观察

目的探讨妇肤康喷雾剂联合乳杆菌活菌胶囊治疗产后阴道炎的临床疗效。方法选取2015年1月—2017年1月郑州市第二人民医院收治的产后阴道炎患者78例,随机分为对照组和治疗组,每组各39例。对照组患者阴道深部放入阴道用乳杆菌活菌胶囊,1粒/次,1次/d。治疗组患者在对照组基础上外阴喷洒妇肤康喷雾剂,3~5揿/次,2次/d。两组均持续治疗10 d。评价两组患者临床疗效,同时比较治疗前后两组患者阴道症状、阴道p H值和复发情况。结果治疗后,对照组和治疗组的临床有效率分别为76.92%和94.87%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者p H值和阴道炎症评分较治疗前显著降低,阴道健康状况评分明显提高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组p H值和阴道炎症评分显著低于对照组,阴道健康状况评分高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组总复发率为5.13%,显著低于对照组的12.82%,两组比较差异具有统计学意义(P0.05)。结论妇肤康喷雾剂联合乳杆菌活菌胶囊治疗产后阴道炎可改善阴道局部微环境,降低复发率,具有一定的临床推广应用价值。     

乳酸杆菌活菌联合特比萘芬治疗念珠菌性阴道炎的疗效观察

目的观察乳酸杆菌活菌联合特比萘芬治疗念珠菌性阴道炎的临床疗效。方法选取2016年1月—2016年12月在中国人民解放军第四五七医院就诊的念珠菌性阴道炎患者106例,随机分为对照组和治疗组,每组各53例。对照组口服盐酸特比萘芬片,0.25 mg/次,1次/d;治疗组在对照组基础上阴道深部放入阴道用乳杆菌活菌胶囊,1粒/次,1次/晚。两组患者均治疗12周。观察两组患者临床疗效,比较治疗前后两组患者临床症状评分和临床症状体征改善时间。结果治疗后,对照组临床总有效率为79.25%,显著低于治疗组的92.45%。两组比较差异具有统计学意义(P0.05)。治疗后,两组患者外阴瘙痒和灼痛感评分均明显降低(P0.05);且治疗组上述临床症状评分比对照组更低(P0.05)。治疗组患者临床症状体征开始改善时间明显短于对照组,两组比较差异具有统计学意义(P0.05)。结论乳酸杆菌活菌联合特比萘芬治疗念珠菌性阴道炎疗效显著,可明显改善患者临床症状,不良反应较少,具有一定的临床推广应用价值。     

Effects of an integrated poultry value chain,nutrition, gender and WASH intervention (SELEVER) on hygiene and child morbidity and anthropometry in Burkina Faso: A secondary outcome analysis of a cluster randomised trial

Nutrition-sensitive agriculture programmes have the potential to improve child nutrition outcomes, but livestock intensification may pose risks related to water, sanitation and hygiene (WASH) conditions. We assessed the impact of SELEVER, a nutrition- and gender-sensitive poultry intervention, with and without added WASH focus, on hygiene practices, morbidity and anthropometric indices of nutrition in children aged 2−4 years in Burkina Faso. A 3-year cluster randomised controlled trial was implemented in 120 villages in 60 communes (districts) supported by the SELEVER project. Communes were randomly assigned using restricted randomisation to one of three groups: (1) SELEVER intervention (n = 446 households); (2) SELEVER plus WASH intervention (n = 432 households); and (3) control without intervention (n = 899 households). The study population included women aged 15−49 years with an index child aged 2−4 years. We assessed the effects 1.5-years (WASH substudy) and 3-years (endline) post-intervention on child morbidity and child anthropometry secondary trial outcomes using mixed effects regression models. Participation in intervention activities was low in the SELEVER groups, ranging from 25% at 1.5 years and 10% at endline. At endline, households in the SELEVER groups had higher caregiver knowledge of WASH-livestock risks (∆ = 0.10, 95% confidence interval [CI] [0.04−0.16]) and were more likely to keep children separated from poultry (∆ = 0.09, 95% CI [0.03−0.15]) than in the control group. No differences were found for other hygiene practices, child morbidity symptoms or anthropometry indicators. Integrating livestock WASH interventions alongside poultry and nutrition interventions can increase knowledge of livestock-related risks and improve livestock-hygiene-related practices, yet may not be sufficient to improve the morbidity and nutritional status of young children.     

Quantification of visits of wild fauna to a commercial free‐range layer farm in the Netherlands located in an avian influenza hot‐spot area assessed by video‐camera monitoring

Free‐range poultry farms have a high risk of introduction of avian influenza viruses (AIV), and it is presumed that wild (water) birds are the source of introduction. There is very scarce quantitative data on wild fauna visiting free‐range poultry farms. We quantified visits of wild fauna to a free‐range area of a layer farm, situated in an AIV hot‐spot area, assessed by video‐camera monitoring. A total of 5,016 hr (209 days) of video recordings, covering all 12 months of a year, were analysed. A total of 16 families of wild birds and five families of mammals visited the free‐range area of the layer farm. Wild birds, except for the dabbling ducks, visited the free‐range area almost exclusively in the period between sunrise and the moment the chickens entered the free‐range area. Known carriers of AIV visited the outdoor facility regularly: species of gulls almost daily in the period January–August; dabbling ducks only in the night in the period November–May, with a distinct peak in the period December–February. Only a small fraction of visits of wild fauna had overlap with the presence of chickens at the same time in the free‐range area. No direct contact between chickens and wild birds was observed. It is hypothesized that AIV transmission to poultry on free‐range poultry farms will predominantly take place via indirect contact: taking up AIV by chickens via wild‐bird‐faeces‐contaminated water or soil in the free‐range area. The free‐range poultry farmer has several possibilities to potentially lower the attractiveness of the free‐range area for wild (bird) fauna: daily inspection of the free‐range area and removal of carcasses and eggs; prevention of forming of water pools in the free‐range facility. Furthermore, there are ways to scare‐off wild birds, for example use of laser equipment or trained dogs.     

囊胚玻璃化冷冻保存时长对复苏移植临床结局的影响

目的研究使用开放式载体玻璃化冷冻保存囊胚的时长对复苏移植妊娠结局和新生儿结局的影响,探讨胚胎经过玻璃化冷冻并进行6年以上的长期保存是否对临床结局产生负面影响。方法回顾性分析2006年3月至2018年12月期间在我院生殖中心进行囊胚玻璃化冷冻复苏移植的2 643例患者的临床资料。按照胚胎玻璃化冷冻保存时长将其分为7组:≤1年,1~2年,2~3年,3~4年,4~5年,5~6年和≥6年,比较各组患者一般情况、临床结局、活产情况和单胎新生儿出生结局之间的差异,再使用二分类Logistic回归分析女性取卵年龄、移植年龄、胚胎冷冻保存时间、囊胚冷冻日期和囊胚级别对妊娠率和活产率的影响。结果各组患者取卵年龄、移植年龄、优胚率、复苏胚胎存活率、妊娠率和活产率组间差异有统计学意义(P<0.05)。各组平均移植胚胎数、D5胚胎比例、种植率、流产率、异位妊娠率、单胎率、出生男孩率、出生缺陷率、单胎出生体重、身长和孕天数均无统计学差异(P>0.05)。Logistic回归分析显示取卵年龄、移植年龄和冷冻保存时间对妊娠率无显著影响(P>0.05),取卵年龄和冷冻保存时长对活产率无显著影响(P>0.05),而增加移植D5胚胎和优质胚胎数量可以提高妊娠率和活产率(P<0.05),移植年龄的增加会降低活产率(P<0.05)。结论使用开放性载体玻璃化冷冻保存囊胚的时长对复苏后移植的妊娠结局和新生儿结局没有明显影响。囊胚经过玻璃化冷冻并进行6年以上长期冷冻保存,临床结局未产生明显负面影响。     

脱氧核苷酸钠干预实体瘤化疗所致骨髓抑制及肝损伤临床观察

目的：评价脱氧核苷酸钠短期大剂量干预实体肿瘤化疗所引起骨髓抑制及肝脏损伤的有效性及安全性,并评价脱氧核苷酸钠对肿瘤细胞生长的影响。方法：86例肺癌、胃癌、结直肠癌、肝癌患者,随机分为对照组和观察组各43例。两组均采用常规化疗方案,观察组在化疗基础上给予脱氧核苷酸钠200mg,ivd,qd。化疗后评价两组患者骨髓抑制、肝功能和体质量情况。结果：观察组与对照组总有效率分别为47.5%,44.9%,差异无统计学意义（P〉0.05）。观察组患者III～IV度骨髓抑制发生率为20.0%,明显低于对照组的58.5%（P〈0.05）;CD3＋、CD4＋、NK细胞水平均高于对照组（P〈0.01）。两组肝功能异常发生率分别为27.5%、65.8%,差异有统计学意义（P〈0.01）。化疗后,观察组患者体质量明显高于对照组（P〈0.05）。结论：脱氧核苷酸可以减轻化疗所导致的骨髓抑制及肝功能的损伤,促进患者体质量恢复。     

Antimicrobial efficacy of a novel silver hydrogel dressing compared to two common silver burn wound dressings: Acticoat™ and PolyMem Silver

A novel burn wound hydrogel dressing has been previously developed which is composed of 2-acrylamido-2-methylpropane sulfonic acid sodium salt with silver nanoparticles. This study compared the antimicrobial efficacy of this novel dressing to two commercially available silver dressings; Acticoat™ and PolyMem Silver^®. Three different antimicrobial tests were used: disc diffusion, broth culture, and the Live/Dead^® Baclight™ bacterial viability assay. Burn wound pathogens (P. aeruginosa, MSSA, A. baumannii and C. albicans) and antibiotic resistant strains (MRSA and VRE) were tested. All three antimicrobial tests indicated that Acticoat™ was the most effective antimicrobial agent, with inhibition zone lengths of 13.9–18.4 mm. It reduced the microbial inocula below the limit of detection (10² CFU/ml) and reduced viability by 99% within 4 h. PolyMem Silver^® had no zone of inhibition for most tested micro-organisms, and it also showed poor antimicrobial activity in the broth culture and Live/Dead^® Baclight™ assays. Alarmingly, it appeared to promote the growth of VRE. The silver hydrogel reduced most of the tested microbial inocula below the detection limit and decreased bacterial viability by 94–99% after 24 h exposure. These results support the possibility of using this novel silver hydrogel as a burn wound dressing in the future.     

H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK

Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.