Uptake and timeliness of rotavirus vaccination in Norway: The first year post-introduction

BackgroundTo minimise vaccine-associated risk of intussusception following rotavirus vaccination, Norway adopted very strict age limits for initiating and completing the vaccine series at the time rotavirus vaccination was included in the national immunisation programme, October 2014. Although Norway has a high coverage for routine childhood vaccines, these stringent age limits could negatively affect rotavirus coverage. We documented the status and impact of rotavirus vaccination on other infant vaccines during the first year after its introduction.MethodsWe used individual vaccination data from the national immunisation register to calculate coverage for rotavirus and other vaccines and examine adherence with the recommended schedules. We identified factors associated with completing the full rotavirus series by performing multiple logistic regression analyses. We also evaluated potential changes in uptake and timeliness of other routine vaccines after the introduction of rotavirus vaccine using the Kaplan-Meier method.ResultsThe national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively. Among fully rotavirus-vaccinated children, 98% received both doses within the upper age limit and 90% received both doses according to the recommended schedule. The child’s age at the initiation of rotavirus series and being vaccinated with diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP/IPV/Hib) and pneumococcal vaccines were the strongest predictors of completing the full rotavirus series. No major changes in uptake and timeliness of other paediatric vaccines were observed after introduction of rotavirus vaccine.ConclusionsNorway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme. Rotavirus vaccination did not impact coverage or timeliness of other infant vaccines.     

Rotavirus,vaccine failure or diagnostic error?

Immunochromatography (ICG) is highly used in clinical settings for rotavirus (RV) diagnosis. The specificity of the tests differs by brand type and is not 100%, therefore its use when the prevalence of the disease is low (i.e. in vaccinated children) may result in a proportion of false positive diagnoses.In some areas, vaccine effectiveness studies or surveillance is done using ICG. Our objective was to estimate the validity of ICG test in vaccinated children, and estimate the number of false positive results in the Valencian Region of Spain, where all RV infections are diagnosed using ICG and are not confirmed by PCR.Population based registries were used to identify all results from the RV antigen tests performed between January 2008 and June 2012 in children under 37 months. Hospitalization and vaccination status of the patients were obtained by linking different databases through a unique identification number. The Positive Predictive Value of the ICG test depending on the vaccination status of the child, hospitalization and the rotavirus season was estimated by a Bayesian model of latent classes.Of the 48,833 tests with valid results, 9429 were done in vaccinated children, and of those 3963 (42%) during the rotavirus season. The prevalence of positive results in vaccinated varied from 2.9 to 21.4% of the tests depending on the hospitalization and seasonality. The estimated PPV also varied from 27.1 to 84.6% when stratified by these two parameters. Globally it is calculated that approximately 267 out of the 520 (51.3%) positives in vaccinated children were false positive tests.The large percentage of false positives, due to an excessive number of tests in vaccinated and out of the RV season, if interpreted as vaccine failures, can cause a loss of confidence in the vaccine and lower the estimates of vaccine effectiveness.     

Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.     

76例轮状病毒性肠炎临床症状观察

目的 :分析 76例轮状病毒 (RV)性肠炎患者的临床症状。方法 :对 76例不同年龄组 RV肠炎患儿的临床症状进行回顾性分析。结果 :1同时出现呼吸系统症状并伴流涕、鼻塞、咳嗽、气促 59例 ;支气管炎 19例 ;肺炎 5例。 2出现抽搐7例。 3生化检查结果门冬氨酸氨基转移酶 (AST)明显增高 76例 ;肌酸激酶 (CK)增高 52例 ;丙氨酸氨基转移酶 (AL T)轻度增高 48例 ;乳酸脱氢酶 (L DH)增高 13例。 4X线胸片肺纹理增粗 8例 ;双肺斑片影 4例。 5心电图表现窦性心动过速 4例 ,T波改变 1例。结论 :RV感染可造成病毒血症 ,且可呈多系统播散 ,使机体各脏器组织损伤 ,致婴幼儿发病。故要对这一弱小群体实行早期预防保健 ,有关部门应引起重视     

Interference of oral poliovirus vaccine on RIT 4237 oral rotavirus vaccine

A vaccination trial, performed on 86 3-month-old infants, has shown that the ability of the RIT 4237 live attenuated rotavirus strain to induce seroconversion is dramatically reduced when administered with live poliovirus vaccine. In a subsequent trial performed on 93 infants the attempt to overcome the poliovirus interference by administering two doses of associated vaccines was unsuccessful. No interference by the RIT 4237 strain on live attenuated polioviruses was observed.     

激光液与654-2联合治疗轮状病毒性肠炎的疗效观察

目的：为评价激光辐射葡萄糖液（简称激光液）与６５４—２联合治疗轮状病毒所致婴幼儿腹泻的疗效。方法：用ＥＬＩＳＡ一步法检查大便轮状病毒阳性２岁以下的腹泻患儿１３２例，随机分为治疗组６３例（激光液与６５４—２联合治疗）和对照组６９例（常规治疗）。结果：治疗组总有效率９０．５％，明显高于对照组５２．２％，两者比较有显著意义（ｘ２＝３４．３６，Ｐ＜０．０１）。结论：激光液与６５４—２联合应用是治疗婴幼儿轮状病毒性肠炎安全有效的方法。     

Human rotavirus specific T cells: quantification by ELISPOT and expression of homing receptors on CD4+ T cells

Using an intracellular cytokine assay, we recently showed that the frequencies of rotavirus (RV)-specific CD4(+) and CD8(+) T cells secreting INFgamma, circulating in RV infected and healthy adults, are very low compared to the frequencies of circulating cytomegalovirus (CMV) reactive T cells in comparable individuals. In children with acute RV infection, these T cells were barely or not detectable. In the present study, an ELISPOT assay enabled detection of circulating RV-specific INFgamma-secreting cells in children with RV diarrhea but not in children with non-RV diarrhea without evidence of a previous RV infection. Using microbead-enriched CD4(+) and CD8(+) T cell subsets, IFNgamma-secreting RV-specific CD8(+) but not CD4(+) T cells were detected in recently infected children. Using the same approach, both CD4(+) and CD8(+) RV-specific T cells were detected in healthy adults. Furthermore, stimulation of purified subsets of PBMC that express lymphocyte homing receptors demonstrated that RV-specific INFgamma-secreting CD4(+) T cells from adult volunteers preferentially express the intestinal homing receptor alpha4beta7, but not the peripheral lymph node homing receptor L-selectin. In contrast, CMV-specific INFgamma-secreting CD4(+) T cells preferentially express L-selectin but not alpha4beta7. These results suggest that the expression of homing receptors on virus-specific T cells depends on the organ where these cells were originally stimulated and that their capacity to secrete INFgamma is independent of the expression of these homing receptors.     

Ca2+ permeability of the plasma membrane induced by rotavirus infection in cultured cells is inhibited by tunicamycin and brefeldin A

Rotavirus infection of cultured cells induces a progressive increase in plasma membrane permeability to Ca2+. The viral product responsible for this effect is not known. We have used tunicamycin and brefeldin A to prevent glycosylation and membrane traffic and study the involvement of viral glycoproteins, NSP4 and/or VP7, in rotavirus-infected HT29 and MA104 cells. In infected cells, we observed an increase of plasma membrane Ca2+ permeability and a progressive depletion of agonist-releasable ER pools measured with fura 2 and an enhancement of total Ca2+ content measured as 45Ca2+ uptake. Tunicamycin inhibited the increase in membrane Ca2+ permeability, induced a depletion of agonist-releasable and 45Ca2+-sequestered pools. Brefeldin A inhibited the increase of Ca2+ permeability and the increase in 45Ca2+ uptake induced by infection. We propose that the glycosylated viral product NSP4 (and/or VP7) travels to the plasma membrane to form a Ca2+ channel and hence elevate Ca2+ permeability.     

A组轮状病毒广州地方株VP7基因序列的比较分析

目的 了解我国轮状病毒G1型广州地方株与标准株及北京G1型地方株VP7基因序列的差异，为我国轮状病毒疫苗的研制提供资料。方法 通过逆转录—聚合酶链反应(RT—PCR)获得了轮状病毒广州地方株R97—196 VP7全基因的cDNA片段，将其克隆入T—A克隆质粒pUCm—T中，构建成重组质粒pUCmT—VP7，对克隆的VP7基因进行序列测定。结果 该地方株的基因核苷酸全长为1062nt，读码框架和以往的研究一致，和北京G1型地方株173的VP7氨基酸序列具有高度同源性(98％)，而与不同血清型标准株间则变异较大(73％—81％)，氨基酸序列中存在的一些高变区和保守功能区与已报道的研究结果一致。从进化角度分析，与轮状病毒标准株Wa株，相距较远。结论 轮状病毒广州地方株R97—196 VP7基因片段属G1型，轮状病毒VP7基因的变异与地域有一定关系。     

聚合酶链反应标记轮状病毒地高辛素探针的初步应用

目的为探讨聚合酶链反应（ＰＣＲ）技术标记的地高辛素（ＤＩＧ）探针的特异性和敏感性。方法用聚合酶链反应技术制备地高辛素标记的人类轮状病毒（ＨＲＶ）ｃＤＮＡ探针，经ｃＤＮＡ－ＲＮＡ斑点杂交。结果该探针具ＨＲＶ特异性，可检出１０ｐｇ的ＲＮＡ。应用该项技术检测了１２０份婴幼儿腹泻粪样标本，其阳性率为６５％，明显高于ＰＡＧＥ方法（４９．１％）的阳性率。结论ＰＣＲ方法直接制备地高辛素标记的ｃＤＮＡ探针方便、快速、特异性好、标记率高。