Effectiveness of the 2012/13 Trivalent Live and Inactivated Influenza Vaccines in Children and Adolescents in Saxony-Anhalt,Germany: A Test-Negative Case-Control Study

A live attenuated influenza vaccine has been available in Germany since the influenza season 2012/13, which is approved for children aged 2-17 years. Using data from our laboratory-based surveillance system, we described the circulation of influenza and non-influenza respiratory viruses during the influenza season 2012/13 in Saxony-Anhalt. We estimated the effectiveness of live and inactivated trivalent influenza vaccines in preventing laboratory-confirmed cases among children and adolescents. From week 40/2012 to 19/2013, sentinel paediatricians systematically swabbed acute respiratory illness patients for testing of influenza and 5 non-influenza viruses by PCR. We compared influenza cases and influenza-negative controls. Among children aged 2-17 years, we calculated overall and vaccine type-specific effectiveness against laboratory-confirmed influenza, stratified by age group (2-6; 7-17 years). We used multivariable logistic regression to adjust estimates for age group, sex and month of illness. Out of 1,307 specimens, 647 (35%) were positive for influenza viruses and 189 (15%) for at least one of the tested non-influenza viruses. For vaccine effectiveness estimation, we included 834 patients (mean age 7.3 years, 53% males) in our analysis. Of 347 (42%) influenza-positive specimens, 61 (18%) were positive for A(H1N1)pdm09, 112 (32%) for A(H3N2) and 174 (50%) for influenza B virus. The adjusted overall vaccine effectiveness including both age groups was 38% (95% CI: 0.8-61%). The adjusted effectiveness for inactivated vaccines was 37% (95% CI: -35-70%) and for live vaccines 84% (95% CI: 45-95%). Effectiveness for the live vaccine was higher in 2-6 year-old children (90%, 95% CI: 20-99%) than in children aged 7-17 years (74%, 95% CI: -32-95%). Our study of the strong influenza season in 2012/13 suggests a high preventive effect of live attenuated influenza vaccine especially among young children, which could not be reached by inactivated vaccines. We recommend the use of live attenuated influenza vaccines in children unless there are contraindications.     

磷酸奥司他韦颗粒联合小儿咳喘灵颗粒治疗小儿季节性流感的临床效果分析

季节性流感多发病于小儿人群,主要是小儿抵抗能力与免疫能力相对低下。季节性流感多发病于春冬季节,且以冬季最为显著。现阶段,临床中为了提升小儿季节性流感的治疗效果,多采用联合用药的治疗方式,效果相对显著。为探讨磷酸奥司他韦颗粒联合小儿咳喘灵颗粒在小儿季节性流感中的应用效果及价值,本研究选取2017年10月至2018年10月我院接收的78例小儿季节性流感患者,依据治疗方法的差异性,设置观察组与对照组,每组39例。对照组为单一磷酸奥司他韦颗粒治疗,观察组为磷酸奥司他韦颗粒联合小儿咳喘灵颗粒治疗。结果显示,两组治疗后症状改善时间的比较差异显著(P<0.05)。治疗后,两组患者的淋巴细胞百分比均较治疗前下降,且观察组的淋巴细胞百分比明显低于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较无统计意义(P>0.05);两组治疗效果具有显著性差异(P<0.05)。本研究提示,两种治疗方案在小儿季节性流感治疗中均能够降低不良反应发生率,其中联合用药治疗方案在缩短症状改善时间的作用更为显著,可提升临床治疗效果,具有突出性应用价值。     

Infection-Triggered Familial or Recurrent Cases of Acute Necrotizing Encephalopathy Caused by Mutations in a Component of the Nuclear Pore, RANBP2

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C→T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.     

甲型流感病毒合并肺部感染与非病毒性肺部感染的表现及治疗分析

目的:通过与非病毒性肺部感染对比,分析甲型流感病毒合并肺部感染患者的常见临床实验检查及治疗效果,为经验性治疗甲型流感病毒提供一定依据。方法:选择2017年11月至2018年4月期间在我科接受治疗的已确诊存在甲型流病毒合并肺部感染(A组)及非病毒性肺感染(B组)各25例,对于确诊的甲型流感患者给予奥司他韦抗病毒治疗一周外,两组均正常给予常规抗感染治疗,对比两组患者的炎症指标白细胞计数、中性粒细胞比例、C-反应蛋白及治疗天数、住院天数、症状消失时间、不良反应发生率。结果:两组患者的CT检查表现无统计学差异(P0.05),A组患者的白细胞计数水平明显低于B组,差异有统计学意义(P0.05),而两组患者的中性粒细胞比例及C反应蛋白水平差异无统计学意义(P0.05)。两组患者的治疗天数及住院天数差异均无统计学意义(P0.05)。两组患者在体温恢复正常时间、咳嗽消失时间、肺部湿罗音消失时间、气促消失时间等比较差异无统计学意义(P0.05)。A组不良反应发生率为16.00%(4/25),B组不良反应发生率为12.00%(3/25),组间差异无统计学意义(P0.05)。结论:甲型病毒性肺部感染常表现为血常规未见异常,常伴发不同程度炎症反应,除常规抗感染治疗外,口服抗病毒药物奥司他韦可促进疾病转归。     

Fatal cases of influenza A(H3N2) in children: insights from whole genome sequence analysis

During the Northern Hemisphere winter of 2003-2004 the emergence of a novel influenza antigenic variant, A/Fujian/411/2002-like(H3N2), was associated with an unusually high number of fatalities in children. Seventeen fatal cases in the UK were laboratory confirmed for Fujian/411-like viruses. To look for phylogenetic patterns and genetic markers that might be associated with increased virulence, sequencing and phylogenetic analysis of the whole genomes of 63 viruses isolated from fatal cases and non fatal "control" cases was undertaken. The analysis revealed the circulation of two main genetic groups, I and II, both of which contained viruses from fatal cases. No associated amino acid substitutions could be linked with an exclusive or higher occurrence in fatal cases. The Fujian/411-like viruses in genetic groups I and II completely displaced other A(H3N2) viruses, but they disappeared after 2004. This study shows that two A(H3N2) virus genotypes circulated exclusively during the winter of 2003-2004 in the UK and caused an unusually high number of deaths in children. Host factors related to immune state and differences in genetic background between patients may also play important roles in determining the outcome of an influenza infection.     

A clinical diagnostic model for predicting influenza among young adult military personnel with febrile respiratory illness in Singapore

Introduction

Influenza infections present with wide-ranging clinical features. We aim to compare the differences in presentation between influenza and non-influenza cases among those with febrile respiratory illness (FRI) to determine predictors of influenza infection.

Methods

Personnel with FRI (defined as fever≥37.5°C, with cough or sore throat) were recruited from the sentinel surveillance system in the Singapore military. Nasal washes were collected, and tested using the Resplex II and additional PCR assays for etiological determination. Interviewer-administered questionnaires collected information on patient demographics and clinical features. Univariate comparison of the various parameters was conducted, with statistically significant parameters entered into a multivariate logistic regression model. The final multivariate model for influenza versus non-influenza cases was used to build a predictive probability clinical diagnostic model.

Results

821 out of 2858 subjects recruited from 11 May 2009 to 25 Jun 2010 had influenza, of which 434 (52.9%) had 2009 influenza A (H1N1), 58 (7.1%) seasonal influenza A (H3N2) and 269 (32.8%) influenza B. Influenza-positive cases were significantly more likely to present with running nose, chills and rigors, ocular symptoms and higher temperature, and less likely with sore throat, photophobia, injected pharynx, and nausea/vomiting. Our clinical diagnostic model had a sensitivity of 65% (95% CI: 58%, 72%), specificity of 69% (95% CI: 62%, 75%), and overall accuracy of 68% (95% CI: 64%, 71%), performing significantly better than conventional influenza-like illness (ILI) criteria.

Conclusions

Use of a clinical diagnostic model may help predict influenza better than the conventional ILI definition among young adults with FRI.     

Follow-up study of type C influenza outbreak in a children's home

A follow-up study of type C influenza in a children's home was made where the first outbreak of type C influenza occurred in March, 1981. During the survey period of 2 years, 2 additional outbreaks occurred in April and October, 1982 and 4 cases of the secondary and 2 cases of the tertiary infections were serologically confirmed. All of the children exposed to the outbreaks, except 2 particular cases who were suffering from German measles, showed similar mild respiratory symptoms characterized by fever and long-lasting nasal discharge, irrespective of primary, secondary, and tertiary infections. No case of inapparent infection was observed. Incubation period was estimated to be not longer than 5 days and the period of virus shedding, to be longer than 22 days. Antibody response in the sera of patients to type C influenza virus was equally good after every infection, although it was not efficient to prevent the succeeding infection. Factors involved in the repeated infections of type C influenza were discussed.     

Risk factors for severe acute lower respiratory tract infection in Bogota, 2001

Severity of acute respiratory infection is higher in developing countries, especially among the socioeconomically underprivileged. Viral pneumonias are more common, especially among children. A prospective hospital-based case control study was undertaken in Bogota between November 2000 and August 2001, aimed to identify factors related to severe low acute respiratory infection (SLARI). Cases were limited to children aged between 2 months and 5 years who filled WHO criteria for SLARI. Controls were children at the same hospital with ARI in a similar age range, but without symptoms of chest drawing. A total of 638 children (277 cases and 361 controls) were included. The most important risk factors included the following: living in borrowed houses (odds ratio (OR) = 2.7; 95% Confidence Interval (CI): 1.06-7.07), sharing the bed (OR = 1.88, CI: 1.0-3.7), living with more than 9 people (OR = 1.82, CI: 1.0-3.51), and living with smokers (OR = 1.4, CI: 1.0-2.05). Of the 114 samples collected (from children at third day after beginning of symptoms), 98 had viruses, sincitial respiratory virus was the most frequently identified virus (41.8%), followed by influenza A virus (3.1%) and influenza B virus (1%). All positive isolates for influenza A and B were sent to the United States Center for Disease Control (CDC) in Atlanta, where they were classified as influenza A/PANAMA/2007/99-like and influenza B/SICHUAN/379/99-like, respectively.     

Effect of vaccination against pneumococcal infection and influenza in children with asthma

Assessment of clinical course of asthma and IgG response in children with asthma immunized with pneumococcal polysaccharide vaccine (Pneumo 23) and influenza vaccine (Vaxigrip). 78 children aged 4 - 17 years old were allocated to two groups. Children from the 1st group were immunized against pneumococcal infection and influenza; children from 2nd group were immunized against pneumococcal infection only. Rate of asthma exacerbations in the 1st group of children decreased by 1.7 times compared with the period before vaccination, whereas the same rate in the 2nd group of children decreased by 1.5 times. It was accompanied by the increase of IgG level to antigens of pneumococcalvaccine in blood, which was observed in both groups. Vaccination did not result in increase of IgE levels. Immunization of children with asthma against pneumococcal infection with polysaccharide vaccine or combined immunization against pneumococcal infection and influenza reduced rate of asthma exacerbations and led to formation of immunity to vaccine strains of Streptococcus pneumoniae. Vaccination did not lead to sensitization of children.     

Differential Pathological and Immune Responses in Newly Weaned Ferrets Are Associated with a Mild Clinical Outcome of Pandemic 2009 H1N1 Infection

Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses.     

Total immunization of children against influenza decreases morbidity in a number of diseases among elderly persons during influenza epidemic

Immunization of children aged 3-6 years in kindergartens and school children aged 7-17 years against influenza with inactivated influenza vaccine was carried out in two districts of the Moscow region. The comparison of morbidity in influenza-like diseases among the immunized children with that among nonimmunized children in control districts revealed that the effectiveness of immunization was 60.9% in kindergartens and 68.8% in schools. The analysis of morbidity in a number of diseases among 158,451 elderly persons not immunized against influenza demonstrated that, in comparison with the control districts, in those districts where mass immunization of children was carried out morbidity in influenza-like diseases among elderly persons was 3.4 times lower and, out of other 10 diseases under study, morbidity in 8 diseases was 1.5-2.6 times lower. As indicated by the data obtained in this study, total anti-influenza immunization of children in organized groups not only essentially decreased influenza morbidity among children, but also greatly decreased morbidity in influenza and a number of diseases, appearing as complications of influenza infection, among nonimmunized elderly persons during influenza epidemic.     

Diagnosis of influenza viruses with special reference to novel H1N1 2009 influenza virus

On 15 April and 17 April 2009, novel swineorigin influenza A (H1N1) virus was identifi ed in specimens obtained from two epidemiologically unlinked patients in the United States. The ongoing outbreak of novel H1N1 2009 influenza (swine influenza) has caused more than 3,99,232 laboratory confi rmed cases of pandemic influenza H1N1 and over 4735 deaths globally. This novel 2009 influenza virus designated as H1N1 A/swine/California/04/2009 virus is not zoonotic swine flu and is transmitted from person to person and has higher transmissibility then that of seasonal influenza viruses. In India the novel H1N1 virus infection has been reported from all over the country. A total of 68,919 samples from clinically suspected persons have been tested for influenza A H1N1 across the country and 13,330 (18.9%) of them have been found positive with 427 deaths. At the All India Institute of Medical Sciences, New Delhi India, we tested 1096 clinical samples for the presence of novel H1N1 influenza virus and seasonal influenza viruses. Of these 1096 samples, 194 samples (17.7%) were positive for novel H1N1 influenza virus and 197 samples (18%) were positive for seasonal influenza viruses. During outbreaks of emerging infectious diseases accurate and rapid diagnosis is critical for minimizing further spread through timely implementation of appropriate vaccines and antiviral treatment. Since the symptoms of novel H1N1 influenza infection are not specifi c, laboratory confi rmation of suspected cases is of prime importance.     

匹多莫德对反复呼吸道感染患儿外周血T淋巴细胞亚群变化的影响及其临床疗效

目的:研究匹多莫德治疗反复呼吸道感染患儿的临床疗效,并探讨其对患儿外周血T淋巴细胞亚群变化的影响。方法:选择我院收治的160例反复呼吸道感染患儿,根据临床治疗方法将其分成研究组(80例)与对照组(80例),对照组采用抗生素或抗病毒、退热、止咳、平喘与化痰等对症治疗,研究组则在对照组的基础上再加用匹多莫德口服。比较两组患儿外周血T淋巴细胞亚群变化并分析其临床疗效。结果:研究组治疗总有效率显著优于对照组(P0.05)。研究组治疗后CD3+、CD4+、CD4+/CD8+水平,与治疗前比较明显升高(P0.05),与对照组同期比较具有明显的差异(P0.05)。研究组患儿治疗后白细胞计数及中性粒细胞水平,与治疗前比较无明显差异(P0.05),与对照组同期比较无明显差异(P0.05);对照组治疗前后白细胞计数及中性粒细胞水平无明显差异(P0.05)。研究组患儿咳嗽、发热、喘息、肺部啰音消失时间以及抗生素使用时间均明显少于对照组(P0.01)。研究组与对照组患儿治疗过程中均未发生明显的药物不良反应。结论:匹多莫德治疗反复呼吸道感染患儿疗效确切,能有效改善T淋巴细胞的免疫功能,值得临床推广与应用。     

Evaluation of the efficacy of split-product trivalent A(H1N1), A(H3N2), and B influenza vaccines: protective efficacy

A total of 1,995 primary school children (1,464 vaccinees and 531 non-vaccinees) were studied to evaluate the protective efficacy of Tween-ether split trivalent A(H1N1), A(H3N2), and B influenza vaccines by comparison of the incidence of confirmed infection in two groups during 1980 to 1984. During the study period, epidemics caused by antigenically different influenza viruses, that is A(H1N1) epidemics in 1981 and 1984, a B epidemic in 1982 and an A(H3N2) epidemic in 1983, were experienced, and at the same time strains changed by antigenic drift were frequently isolated. In these epidemics, 61% to 87% of the children reported respiratory illnesses and 18% to 48% of the illnesses were influenza confirmed by seroconversion. Throughout these four epidemics, the incidence of confirmed infection among the vaccinees (7.8% to 33.8%) was 6.5% to 34.8% lower than that among the nonvaccinees (35.4% to 51.6%), demonstrating that the vaccine was effective (X2 = 76.34, P less than 0.001). However, this effectiveness was not seen in an epidemic in one of the entrant schools in 1984, possibly caused by a strain with intense antigenic drift. On the basis of data on incidence of various symptoms, duration of fever and the number of days of absence from class, it was considered that clinical symptoms in the vaccinees were milder than those in the nonvaccinees. When the titers of hemagglutination-inhibiting (HAI) antibody against the vaccine strains were measured, the protective level of HAI antibody giving less than or equal to 50% incidence of infection was 1:64, but it increased to 1:256 in the 1984 epidemic, reflecting the high rate of isolates with intense antigenic drift.     

帕拉米韦氯化钠注射液对流感病毒A型肺炎患儿的成本-效益分析

目的:探讨帕拉米韦氯化钠注射液对流感病毒A型肺炎患儿的成本-效益。方法:选择我院2015年1月至2018年12月收治的96例流感病毒A型肺炎患儿,根据随机数字表法,将96例患儿分为A组及B组,每组48例,A组患儿给予磷酸奥司他韦颗粒,B组患儿给予帕拉米韦氯化钠注射液,对比两组患儿的治疗效果、临床症状消失时间、住院时间、用药成本、成本-效益,对比两组患儿治疗前及治疗后的血常规及肝肾功能,对比两组患儿的不良反应发生率。结果:B组患儿的治疗有效率明显较A组高(P<0.05)。观察组患儿的临床症状消失时间及住院时间明显较对照组低(P<0.05)。A组患儿的平均用药成本明显低于B组(P<0.05),A组的成本-效益较B组低。与治疗前相比,治疗后两组患儿的中性粒细胞总数明显升高,白细胞总数、淋巴细胞总数明显降低(P<0.05);而治疗前后,两组患儿的血常规指标对比无统计学意义(P>0.05)。治疗前后,两组患儿的肝肾功能对比均无统计学意义(P>0.05)。B组患儿的不良反应发生率较A组高,但组间对比无统计学意义(P>0.05)。结论:与磷酸奥司他韦相比,帕拉米韦氯化钠注射液对流感病毒A型肺炎患儿的疗效更佳,但其成本-效益较低,临床上可根据患儿实际情况选择用药。     

The role of respiratory tract viruses in the etiology of obstructive bronchitis in infants

Out of 524 children with acute respiratory infections in 141 obstructive bronchitis was diagnosed (OZO). Seventy cases could be linked to viral infection. Viral infections tested (influenza virus A, B, parainfluenza typ 1-3, RSV, adenoviruses) were more frequently associated with OZO than other acute respiratory infections of unknown etiology. Majority infections induced by influenza virus A and parainfluenza virus typ 2 were accompanied by OZO symptoms. Of the highest risk of acquiring OZO despite of viral infection participation, were children of 4-12 months of age. OZO associated viral infections prevailed during autumn-winter season, while in spring-summer period undetermined factors were the major cause of OZO. In serum samples of children with OZO, despite of etiology of the disease, higher level of IgE was found than in a group of children without the symptoms. In the case of OZO of unestablished etiology the level of serum IgE was significantly higher than in the cases when viral etiology of the disease was found.     

Dengue and Chikungunya Fever among Viral Diseases in Outpatient Febrile Children in Kilosa District Hospital,Tanzania

Introduction

Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria.

Methods

A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2–13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used.

Results

A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35–3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus.

Conclusion

Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.     

闽南地区5 869例儿童社区获得性肺炎患者 病原学特点分析

目的通过对闽南地区社区获得性肺炎(CAP)患儿病原特点进行分析,为CAP早期预警、预防和早期经验治疗提供指导和依据。方法收集我院2015年1月至2017年5月5 869例CAP患儿静脉血、呼吸道分泌物及痰标本分别进行肺炎支原体(MP)、呼吸道病毒检测以及细菌培养和鉴定。结果 5 869例CAP患儿中明确病原体感染4 931例,其中单纯细菌感染3 054例,单纯病毒感染966例,单纯MP感染620例,混合感染291例,未检出病原体938例。细菌性病原主要以肺炎链球菌、流感嗜血杆菌和卡他莫拉菌为主,在各季节检出率不同且男性多于女性,主要在低龄儿童中检出。病毒感染者主要分布于低龄儿童,夏季检出率最高,病原以呼吸道合胞病毒(RSV)为主,占68.22%。该类患者在性别上比较差异无统计学意义。MP感染者中女性多于男性,主要分布于大龄儿童,冬季检出率最高。结论本地区CAP患儿病原检出率由高到低分别为细菌、病毒和MP。细菌和MP检出率在患儿中具有性别差异,各种病原在不同年龄段儿童及季节中检出率不同。