Immunogenicity of a recombinant fusion construct composed of intrinsically unstructured,low polymorphic segments derived from merozoite surface protein 2 and trophozoite exported protein 1

To overcome the extensive polymorphism found in human Plasmodium antigens and to avoid the lengthy characterization of their 3 dimensional structure and subsequent production of the native proteins we have been concentrated in large unstructured, non-or low-polymorphic fragments present in the blood stage of P. falciparum. Three fragments derived from the 2 family-specific and constant regions of merozoite surface protein (MSP2) and PFF0165c protein were previously selected for evaluation as potential single vaccine candidates. In order to increase and optimize their potential efficacy against P. falciparum infection the 3 antigens were combined in a single DNA recombinant product (FusN) and compared its antigenicity with that of single antigens in sera of volunteers living in endemic countries. Immunogenicity of the FusN was then compared with that of the mixture of 3 antigens in 3 strains of mice. Antigen specific, affinity purified human antibodies were then tested in antibody dependent cellular inhibition and merozoite opsonization assays. In addition, the antigen specific antibody response and its association with protection from malaria infection were determined. The data collected indicate that the recombinant product is an equal or better antigen /immunogen than fragments used either alone or as a mixture for vaccination in combination with adjuvant. In addition, antibody response to FusN shows a stronger association with protection than single fragments. The use of a single construct as vaccine would drastically reduce the cost of manufacturing and development of the GMP product.     

Effects of home-based Voluntary Counselling and Testing on HIV-related stigma: Findings from a cluster-randomized trial in Zambia

HIV-related stigma continues to be a prominent barrier to testing, treatment and care. However, few studies have investigated changes in stigma over time and the factors contributing to these changes, and there is no evidence of the impact of HIV testing and counselling on stigma. This study was nested within a pair-matched cluster-randomized trial on the acceptance of home-based voluntary HIV counselling and testing conducted in a rural district in Zambia between 2009 and 2011, and investigated changes in stigma over time and the impact of HIV testing and counselling on stigma. Data from a baseline survey (n = 1500) and a follow-up survey (n = 1107) were used to evaluate changes in stigma. There was an overall reduction of seven per cent in stigma from baseline to follow-up. This was mainly due to a reduction in individual stigmatizing attitudes but not in perceived stigma. The reduction did not differ between the trial arms (β = −0.22, p = 0.423). Being tested for HIV was associated with a reduction in stigma (β = −0.57, p = 0.030), and there was a trend towards home-based Voluntary Counselling and Testing having a larger impact on stigma than other testing approaches (β = −0.78, p = 0.080 vs. β = −0.37, p = 0.551), possibly explained by a strong focus on counselling and the safe environment of the home. The reduction observed in both arms may give reason to be optimistic as it may have consequences for disclosure, treatment access and adherence. Yet, the change in stigma may have been affected by social desirability bias, as extensive community mobilization was carried out in both arms. The study underscores the challenges in measuring and monitoring HIV-related stigma. Adjustment for social desirability bias and inclusion of qualitative methods are recommended for further studies on the impact of HIV testing on stigma.     

Influenza vaccine uptake in the elderly population: Individual and general practitioner’s determinants in Central Italy,Lazio region, 2016–2017 season

BackgroundElderly people are a priority target group for influenza vaccination and their decision to be vaccinated might partly depend on advice received from general practitioners (GP). This study aims to investigate the association between influenza vaccine uptake in the elderly residents in the Lazio region of Italy and the demographic and professional characteristics of their GPs, taking simultaneously into account the elderly’s individual characteristics.MethodsWe used data retrieved from different administrative sources to retrospectively analyse the cohort of 1,255,657 elderly residents aged ≥65 years who were alive and registered in the regional healthcare service at the beginning of the 2016–2017 influenza vaccination campaign (1 Oct. 2016–31 Jan. 2017). We assessed influenza vaccine uptake at the end of the vaccination campaign and evaluated its association with both individual and GP-related characteristics through a multilevel Poisson regression models accounting for clustering at physician level.ResultsOverall, vaccination coverage at the end of vaccination campaign was 50.6%. Elderly residents who were male, older, vaccinated in the previous seasons, living in smaller provinces, and spending more money for specialist medical care showed a significantly increased probability to be vaccinated. Vaccine uptake was also significantly higher in the elderly residents assisted by GPs who got master’s degree more recently, assisted a relatively high proportion of elderly patients, received influenza vaccination, had a computer assistant, and were associated with other physicians.ConclusionsOur results indicate that influenza vaccination coverage in the elderly residents of the Lazio region is still unsatisfactorily low. We identified several determinants of influenza vaccine uptake, related to both individual and GP characteristics. Understanding how GP characteristics affected influenza vaccine uptake in the elderly population might provide insight on GPs’ attitudes and concerns regarding influenza vaccination, allowing the implementation of targeted evidence-based interventions to sensitise GPs and increase vaccination coverage.     

Molecular characteristics of Salmonella enterica Paratyphi A in Yunnan Province,southwest China

Previously, the prevalence of Salmonella enterica Paratyphi A in Yunnan was high; and recently Yunnan was the predominant endemic province in China. To identify the molecular epidemiology, antibiotic resistance profile and genotypic diversity of the S. Paratyphi A isolates from 1995 to 2013 in Yunnan, we performed the study. Antibiotic susceptibility tests, pulse-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were used to identify the characteristics of the bacterial isolates. The results showed from 1995 to 2013, 366 S. Paratyphi A were isolated: 295 isolates (80.6%) from Yuxi and 68 isolates (18.58%) from Honghe. All of the strains were resistant to nalidixic acid, and some were resistant to ampicillin and trimethoprim/sulfamethoxazole in different years. All the isolates were sensitive to cefotaxime and ciprofloxacin. Identical PFGE with two enzyme digestion patterns were found for 339 isolates. Some environmental isolates in different years were homologous with the strains isolated from food and patients. MLST showed 349 strains were ST85, only 17 isolates were ST129. S. Paratyphi A isolates from Yunnan showed a high similarity, and we found the pathogen isolated from patients, the environment and food had the close epidemiological relationship, forming a transmission circulation. These findings have important implications for paratyphoid-control strategies.     

PED subunit vaccine based on COE domain replacement of flagellin domain D3 improved specific humoral and mucosal immunity in mice

Porcine epidemic diarrhea (PED) is an important re-emergent infectious disease and inflicts huge economic losses to the swine industry worldwide. To meet the pressing need of developing a safe and cost-efficient PED maternal vaccine, we generated three PED subunit vaccine candidates, using recombined Salmonella flagellin (rSF) as a mucosal molecular adjuvant. Domain D3 in rSF was replaced with COE domain of PEDV to generate rSF-COE-3D. COE fused to the flanking C′/N′ terminal of rSF yielded rSF-COE-C and rSF-COE-N. As a result, rSF-COE-3D could significantly improve COE specific antibody production including serum IgG, serum IgA, mucosal IgA and PEDV neutralizing antibody. Furthermore, rSF-COE-3D elicited more CD3⁺CD8⁺ T cell and cytokine production of IFN-γ and IL-4 in mouse splenocytes. In summary, our data showed that rSF-COE-3D could improve specific humoral and mucosal immunity in mice, thus suggesting that rSF-COE-3D could be applied as a novel efficient maternal PED vaccine.     

浙江省2005-2020年肾综合征出血热流行趋势分析

目的 了解浙江省2005-2020年肾综合征出血热（HFRS）流行特征和时空分布特征,为其精准防控提供科学依据。方法 从中国疾病预防控制传染病报告信息管理系统获取疫情数据,通过描述性研究了解浙江省HFRS的三间分布特征;采用ArcGIS 10.2软件进行全局自相关和局部自相关分析;采用SaTScan 9.4.4软件进行时空聚集区扫描分析,ArcGIS 10.2软件完成疾病时空分布的可视化。结果 浙江省2005-2020年共报告7 724例HFRS病例,其中死亡25例。每年有2个发病高峰,分别在5-6月（春末夏初）和11月至次年1月（冬季）。累计病例在前三位的地市分别是宁波市24.27%（1 875/7 724）、台州市21.25%（1 642/7 724）和绍兴市14.54%（1 123/7 724）。男女性别比为2.73：1（5 656：2 068）。病例主要以中老年为主,41~70岁的病例占60.95%。职业主要是农民,占69.89%（5 398/7 724）。大多数年份HFRS的空间分布存在相关性,回顾性时空扫描结果显示,探测到3个聚集区：一类聚集区集中在浙江省东部和中部地区的21个县（市、区）,其中宁波市、绍兴市和金华市各有4个县（市、区）、台州市8个县（市、区）和丽水市1个县（RR=13.69,LLR=5 522.60,P<0.001）;二类聚集区集中在浙江省西部地区丽水市的龙泉市和庆元县（RR=31.20,LLR=1 232.46,P<0.001）;三类聚集区集中在浙江省北部地区湖州市的长兴县和安吉县（RR=3.42,LLR=23.93,P<0.001）。结论 2005-2020年浙江省HFRS病例以中老年、男性和农民为主,在春末夏初和冬季的东部地区疫情高发,建议重点地区在流行季节来临前针对重点人群采取精准防控措施。