Vaccine efficacy against Indonesian Highly Pathogenic Avian Influenza H5N1: systematic review and meta-analysis

Indonesia has implemented multiple strategies to control Highly Pathogenic Avian Influenza H5N1 (HPAI/H5N1), including the licensure and use of multiple vaccine formulations. The continuous drift of Indonesian HPAI/H5N1 viruses and emergence of a new clade in 2012 that became dominant in 2016, demands the assessment of commercial vaccine formulations against Indonesian field viruses.Seven databases were explored to identify relevant literature reporting performance of commercial vaccines against Indonesian HPAI/H5N1 viruses. After methodological assessment, data were collated and analyzed to report immunogenicity and vaccine efficacy (VE) to prevent respiratory and cloacal viral shedding 2-day post challenge, and death at the end of the follow-up period. Meta-analyses were performed to assess VE consistency of alternative formulations and to explore sources of heterogeneity in VE.In total, 65 studies and 46 vaccine formulations from 13 articles were grouped per OIE's VE protocols (group 1) and variations of it (groups 2,3,4). We found that concurrence of vaccine-seed and challenge-viruses in a clade designation might be a better proxy of VE than current estimates based on vaccine-homologous HI antibody titers, particularly against current fourth order clade viruses (groups 1&2). Prime-boosting was efficacious across different chicken breeds (group 3), and early vaccination may increase the risk of death (group 4). One Indonesian vaccine was tested against the new dominant clade, conferring consistent protection in chickens but not in ducks. Meta-analyses revealed high inconsistency (I² ≥ 75%) and inefficacy of LPAI formulations against current field viruses, while potential sources of inconsistent VE were formulation of seed-homologous vaccines and the species vaccinated.We conclude that the VE of commercial vaccines in Indonesia changes as Indonesian HPAI/H5N1 evolve into new clades, which should warrant continuous matching between vaccine-seeds and emerging HPAI/H5N1. Furthermore, given the characteristics of the new Indonesian dominant HPAI/H5N1 clade, further studies to confirm VE across species are warranted.     

A model for extending the reach of the traditional dental practice: the ForsythKids program

BACKGROUND: The authors describe and evaluate the short-term effectiveness of a community-based program for dental caries prevention in children. METHODS: The authors enrolled pupils in the ForsythKids program after receiving informed consent. They targeted children at six Massachusetts elementary schools, grades 1 through 3, with pupil populations at high risk of developing caries. The children underwent examination by dentists using calibrated technique and received comprehensive preventive care from dental hygienists. The authors determined effectiveness by means of comparing results of the initial examination with those of a second examination performed six months later. RESULTS: At baseline, 70 percent of the 1,196 participating children had decayed or filled teeth. More troublingly, 42.1 percent of the primary teeth and 31.1 percent of the permanent teeth had untreated decay. Six months after preventive intervention, the proportion of teeth with new decay was reduced 52 percent in primary teeth and 39 percent in permanent teeth. Furthermore, the percentage of children with newly decayed or restored primary and permanent teeth was reduced by 25.4 percent and 53.2 percent, respectively. CONCLUSIONS: These results indicate that this care model relatively quickly can overcome multiple barriers to care and improve children's oral health. CLINICAL IMPLICATIONS: If widely implemented, comprehensive caries prevention programs such as ForsythKids could accomplish national health goals and reduce the need for new care providers and clinics.     

Efficacy of multivalent recombinant herpesvirus of turkey vaccines against high pathogenicity avian influenza,infectious bursal disease,and Newcastle disease viruses

Vaccines are an essential tool for the control of viral infections in domestic animals. We generated recombinant vector herpesvirus of turkeys (vHVT) vaccines expressing computationally optimized broadly reactive antigen (COBRA) H5 of avian influenza virus (AIV) alone (vHVT-AI) or in combination with virus protein 2 (VP2) of infectious bursal disease virus (IBDV) (vHVT-IBD-AI) or fusion (F) protein of Newcastle disease virus (NDV) (vHVT-ND-AI). In vaccinated chickens, all three vHVT vaccines provided 90–100% clinical protection against three divergent clades of high pathogenicity avian influenza viruses (HPAIVs), and significantly decreased number of birds and oral viral shedding titers at 2 days post-challenge compared to shams. Four weeks after vaccination, most vaccinated birds had H5 hemagglutination inhibition antibody titers, which significantly increased post-challenge. The vHVT-IBD-AI and vHVT-ND-AI vaccines provided 100% clinical protection against IBDVs and NDV, respectively. Our findings demonstrate that multivalent HVT vector vaccines were efficacious for simultaneous control of HPAIV and other viral infections.     

Mitigation strategies to reduce the generation and transmission of airborne highly pathogenic avian influenza virus particles during processing of infected poultry

Airborne transmission of H5N1 highly pathogenic avian influenza (HPAI) viruses has occurred among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry, and such transmission has been experimentally reproduced. In this study, we investigated simple, practical changes in the processing of H5N1 virus-infected chickens to reduce infectious airborne particles and their transmission. Our findings suggest that containing the birds during the killing and bleeding first step by using a disposable plastic bag, a commonly available cooking pot widely used in Egypt (halla), or a bucket significantly reduces generation of infectious airborne particles and transmission to ferrets. Similarly, lack of infectious airborne particles was observed when processing vaccinated chickens that had been challenged with HPAI virus. Moreover, the use of a mechanical defeatherer significantly increased total number of particles in the air compared to manual defeathering. This study confirms that simple changes in poultry processing can efficiently mitigate generation of infectious airborne particles and their transmission to humans.     

流动注射——分光光度法快速测定儿童发锌含量

介绍流动注射（ＦＩＡ）—分光光度法快速测定微量锌的方法，并研究了ＦＩＡ—分光光度法测定发锌含量的实验条件，实际测定了１６２名２～６岁学龄前男女儿童头发中锌含量，平均回收率为９９．３％±０．６３，精密度ＲＳＤ＝０．４１％。     

Protection of White Leghorn chickens by U.S. emergency H5 vaccination against clade 2.3.4.4 H5N2 high pathogenicity avian influenza virus

During December 2014–June 2015, the U.S. experienced a high pathogenicity avian influenza (HPAI) outbreak caused by clade 2.3.4.4 H5Nx Goose/Guangdong lineage viruses with devastating consequences for the poultry industry. Three vaccines, developed based on updating existing registered vaccines or currently licensed technologies, were evaluated for possible use: an inactivated reverse genetics H5N1 vaccine (rgH5N1) and an RNA particle vaccine (RP-H5), both containing the hemagglutinin gene of clade 2.3.4.4 strain, and a recombinant herpesvirus turkey vectored vaccine (rHVT-H5) containing the hemagglutinin gene of clade 2.2 strain. The efficacy of the three vaccines, alone or in combination, was assessed in White Leghorn chickens against clade 2.3.4.4 H5N2 HPAI virus challenge. In Study 1, single (rHVT-H5) and prime-boost (rHVT-H5 + rgH5N1 or rHVT-H5 + RP-H5) vaccination strategies protected chickens with high levels of protective immunity and significantly reduced virus shedding. In Study 2, single vaccination with either rgH5N1 or RP-H5 vaccines provided clinical protection in adult chickens and significantly reduced virus shedding. In Study 3, double rgH5N1 vaccination protected adult chickens from clinical signs and mortality when challenged 20 weeks post-boost, with high levels of long-lasting protective immunity and significantly reduced virus shedding. These studies support the use of genetically related vaccines, possibly in combination with a broad protective priming vaccine, for emergency vaccination programs against clade 2.3.4.4 H5Nx HPAI virus in young and adult layer chickens.     

呼气末正压通气对小儿心内直视手术后血液动力学的影响

目的：呼气末正压通气（ＰＥＥＰ）是治疗心内直视手术后呼吸功能不全的主要方法之一。但是，较高的ＰＥＥＰ对患者的血液动力学有显著影响。本文探讨了小儿心内直视手术后不同的ＰＥＥＰ对患儿血液动力学的影响及其机制。方法：本实验采用置入Ｓｗａｎ－Ｇａｎｚ导管，对１４例小儿（１．５～５岁）心内直视手术后不同的ＰＥＥＰ下血液动力学指标的变化进行监测，并将数据输入ｄＢａｓｅＩＩ数据库，做自身配对ｔ检验及直线相关与回归分析。结果：当ＰＥＥＰ为０～０．６ｋＰａ（０～６ｃｍＨ２Ｏ）时，对血液动力学无显著影响（Ｐ＞０．０５）；当ＰＥＥＰ≥０．９ｋＰａ（９ｃｍＨ２Ｏ）时，可以引起心脏指数和氧运送的显著下降（Ｐ＜０．０１）。结论：当ＰＥＥＰ≥０．９ｋＰａ（９ｃｍＨ２Ｏ）时，通过减少心脏前负荷，抑制心脏收缩功能，导致心脏指数和氧运送显著下降。因此，临床上需使用较高的ＰＥＥＰ时，应做血液动力学和血气分析监测，以选择最佳的ＰＥＥＰ。     

弱氦氖激光血管内照射治疗缺血性脑卒中临床试验文献评价

目的:了解中国弱氦氖激光血管内照射(intravascularlowleverHe-Nelaserirradiationonblood,ILIB)治疗缺血性脑卒中(cerebralischemicstroke,CIS)随机对照试验和临床对照试验(RCTs/CCTs)的现状,为其系统评价提供线索。方法:通过机检和手检获得发表的RCTs/CCTs共64篇,对文献的随机化分配方法、盲法采用、样本含量、患者纳入标准和排除标准、疗效判定标准、不良反应报告、治疗依从性、随访、失访报告等进行分析。结果:具有明确随机方法仅1篇占2%(1/64),有明确半随机方法3篇占5%(3/64),仅有1篇采用盲法,只有1篇运用空白对照,纳入/排除标准明确占6%,诊断标准明确占94%,疗效判定标准明确占100%,提及不良反应占12%,失访报告占3%,无一篇涉及随访和意向性分析。结论:按Jadad(Jadad1996)和Schulz(Schulz1995)提出的评价文献的质量标准,所调查的文献均存在高度偏倚,仅只有两个研究Jadad评分为2分。中国ILIB治疗CIS的RCTs/CCTs的质量有待进一步提高。     

精氨酸对体外循环术后白细胞介素2变化的影响

目的：探讨精氨酸增强体外循环术后细胞免疫功能是否系促进术后白细胞介素２的产生所致。方法：６０例体外循环手术病人分为两组，每组３０例。精氨酸组术前３天至术后７天每日静脉滴注精氨酸。于术前及术后１、３、５、７、１４天等时点抽外周血按Ｓｔａｎｄｌｅｒ法测定白细胞介素２水平。结果以均数±标准差表示，采用ｔ检验分析差异显著性。结果：对照组术后白细胞介素２水平明显下降，从术前７２．０±３．５（Ｕ／Ｌ，下同）降至术后第５天２９．１±５．２，第７天３５．８±３．９，约２周恢复正常。用药组下降幅度较小，术后第５天４６．７±４．２，第７天７０．１±４．４（组间差异Ｐ＜０．０５），约１周已接近术前水平。结论：精氨酸对体外循环术后白细胞免疫功能恢复具有明显的促进作用，增加术后白细胞介素２的产生可能是其重要机制。     

心脏直视手术后心包及纵隔引流血的分析（附18例报告）

目的：为心脏直视手术后回输未经洗涤的心包及纵隔引流血提供可靠依据。方法：对１８例心脏直视手术后心包及纵隔引流血和１１例库血进行检测，并对各项结果进行Ｆ检验。结果：术后４小时及６小时心包及纵隔引流血分别占术后２４小时引流血量的５０．７％（３６０±９５ｍｌ）及５７．７％（４３０±１００ｍｌ）。心脏手术后病人血及其引流血经需氧菌及厌氧菌培养均阴性。引流血红细胞压积０．３１，库血０．３４（Ｐ＞０．０５）。引流血纤维蛋白降解产物（ＦＤＰ）２３１μｇ／ｍｌ，库血１２５０μｇ／ｍｌ（Ｐ＜０．０５），说明引流血的纤溶活性明显低于库血。ＶＩＩ因子测定，引流血虽较正常值低，但较库血略高。引流血中游离血红蛋白明显高于库血，分别为１３３８±４０６ｍｇ／Ｌ及２１８±８７ｍｇ／Ｌ（Ｐ＜０．０５）。结论：心脏直视手术后的纵隔及心包引流血回输是安全的。