Economic evaluation of typhoid vaccination in a prolonged typhoid outbreak setting: The case of Kasese district in Uganda

BackgroundVaccination has been increasingly promoted to help control epidemic and endemic typhoid fever in high-incidence areas. Despite growing recognition that typhoid incidence in some areas of sub-Saharan Africa is similar to high-incidence areas of Asia, no large-scale typhoid vaccination campaigns have been conducted there. We performed an economic evaluation of a hypothetical one-time, fixed-post typhoid vaccination campaign in Kasese, a rural district in Uganda where a large, multi-year outbreak of typhoid fever has been reported.MethodsWe used medical cost and epidemiological data retrieved on-site and campaign costs from previous fixed-post vaccination campaigns in Kasese to account for costs from a public sector health care delivery perspective. We calculated program costs and averted disability-adjusted life years (DALYs) and medical costs as a result of vaccination, to calculate the cost of the intervention per DALY and case averted.ResultsOver the 3 years of projected vaccine efficacy, a one-time vaccination campaign was estimated to avert 1768 (90%CI: 684–4431) typhoid fever cases per year and a total of 3868 (90%CI: 1353–9807) DALYs over the duration of the immunity conferred by the vaccine. The cost of the intervention per DALY averted was US$ 484 (90%CI: 18–1292) and per case averted US$ 341 (90%CI: 13–883).ConclusionWe estimated the vaccination campaign in this setting to be highly cost-effective, according to WHO's cost-effective guidelines. Results may be applicable to other African settings with similar high disease incidence estimates.     

Production and purification of an active CRM197 in Pichia pastoris and its immunological characterization using a Vi-typhoid antigen vaccine

CRM197 is a commonly used glycoconjugate carrier that improves the immunogenicity of vaccines, particularly in infants. Despite the advantages of this diphtheria toxoid mutant, low yields, production in inclusion bodies, and the requirement for specific growth conditions have limited the breadth of successful recombinant protein expression platforms available for its expression. We evaluated Pichia pastoris as a production host, using the methanol inducible AOX1 promoter and a modified α-mating factor signal peptide for secretion into the supernatant. Final purified yields >100 mg L⁻¹ culture were achieved when produced in a bioreactor, which is equivalent to the productivity obtained from bioprocesses using the native Corynebacterium diphtheriae host. Recombinant CRM197 was purified to ≥95% homogeneity and showed the expected endonuclease activity. Furthermore, mice immunized with a Salmonella enterica serovar Typhi capsular Vi antigen conjugated to our recombinant CRM197 showed greater than 5-fold increase in immune response. Overall, the results demonstrate that Pichia pastoris is a suitable expression host for the production of high quality CRM197 for vaccine applications.     

Should close contacts of returning travellers with typhoid fever be protected by vaccination?

Increasing international travel to areas endemic for typhoid fever correlates with increased risk for travellers to contract the disease. At home, the acutely ill/convalescent patients may pose some risk to their close contacts. In Finland an unofficial guideline suggests vaccination for close contacts of patients with acute typhoid fever; in other developed countries, routine typhoid vaccinations are only recommended to contacts of chronic carriers. This paper discusses the possibilities and limitations of prophylactic/post-exposure typhoid vaccination for contacts of patients with acute disease.     

当归四逆汤异病同治

当归四逆汤出自《伤寒论》,是血虚寒凝的代表方。由当归、桂枝、白芍、大枣、细辛、通草、甘草组成,诸药配合,有和厥阴以散寒邪之功,调营卫以通阳气之效。临证抓住血虚寒凝发病机制,在温经养血活血,通脉散寒止痛治疗原则指导下,灵活运用,随证加减,治疗雷诺氏病、痹证、妇科疾病、肢端动脉硬化闭塞症、荨麻疹,均获满意疗效。显示＂异病同治＂和＂古方新用＂巨大潜力。     

伤寒副伤寒发病趋势的ARIMA模型和GM（1,1）模型预测

目的采用求和自回归滑动平均模型（ARIMA模型）和灰色模型GM（1,1）分别对常州市伤寒副伤寒发病率进行预测,并比较两者预测的准确性。方法根据2001—2010年的月发病率数据分别建立ARIMA模型和GM（1,1）模型。通过比较2011年实际发病率和模型预测发病率间的相对误差验证模型预测的准确性。采用准确性高的模型预测2012—2013年伤寒副伤寒的年发病率。结果 GM（1,1）模型对伤寒副伤寒的年发病率预测准确率较高。2012年和2013年伤寒副伤寒预测的年发病率分别为2.52/105和2.33/105。结论对于伤寒副伤寒发病率的预测,应同时拟合几种模型,选择拟合效果最好的一种模型。     

桂林地区学校伤寒副伤寒干预效果分析

目的用综合干预措施实现伤寒副伤寒干预效果及干预净效应的评价,为校区伤寒副伤寒的防制提供科学依据。方法采用整群分层配对的方法把研究区内符合条件的学校分为干预组和对照组,并对干预组采取水源消毒、卫生管理、健康教育等综合干预措施,通过比较干预前后的变化了解干预的效果以及干预的净效应。结果实施综合干预措施后,干预学校发病率为23／10万,较对照学校147／10万,有统计学意义,保护率为84．35％,效果指数IE为6．39,成本效益比为1：7．08。结论饮用水定期消毒和健康教育等投入小的干预措施在校区内容易实施,也能够明显降低伤寒副伤寒发病率,是有效防制措施。     

Validation of the Dri-Dot Latex agglutination and IgM lateral flow assays for the diagnosis of typhoid fever in an Egyptian population

Laboratory confirmation of typhoid fever is essential for appropriate medical treatment. Blood culture is a standard test for diagnosis of typhoid fever, but well-equipped diagnostic facilities to perform culture are seldom available in endemic areas. We retrospectively compared 2 diagnostic field tests, a latex agglutination Dri-Dot assay and an IgM Lateral Flow assay, to blood culture, in patients with clinically diagnosed typhoid fever. Sensitivity of the Dri-Dot was 71.4%, and specificity was 86.3% for samples collected at time of first diagnosis. Sensitivity and specificity of IgM Lateral Flow were 80% and 71.4%, respectively. A major limitation of these serologic tests is the limited sensitivity at the early stage of the disease. Performing both tests in parallel increased sensitivity to 84.3%, but decreased specificity to 70.5%. There was a trend towards improved diagnostic performance using either assay over a longer duration of illness. These rapid, point-of-care assays for typhoid fever provide easy-to-interpret results in typhoid-endemic countries and may be most useful in patients presenting 1 week after symptom onset.     

小儿伤寒60例误诊分析

目的探讨小儿伤寒误诊的原因,减少误诊率。方法收集1995年1月~2010年月6月收治住院确诊的93例小儿伤寒病例中,初诊误为其他病种的患儿60例进行分析。结果 93例小儿伤寒中误诊为非伤寒者60例,误诊率为64.5%,以误诊上呼吸道感染最多（29例）,肺炎（9例）,支气管炎、菌痢、败血症（4~5例）,病毒性心肌炎、病毒性肝炎、贫血原因待查、肺结核、传染性单核细胞增多症和川崎病（1~2例）。结论详细收集病史,仔细体检,动态观察体征的变化,常规计数嗜酸性粒细胞和肥达反应,及时做血培养及粪培养等实验室检查是减少误诊、漏诊的关键。