禽流感危机及其应对策略

1997～2003年,以往仅感染禽类的禽流感(avian influenza)H5N1、H9N2、H7N7病毒却在我国香港、广东地区及荷兰分别引起人类疫情爆发或个案感染。2003年底至2004年初,亚洲有8个国家出现了禽流感H5N1爆发疫情,且在越南、泰国再次出现人感染禽流感H5N1病毒,其中死亡18例(截止2004年2月10日的数据),引起全球高度关注。在短短的几年时间里,先后发生禽流感     

Attributable deaths due to influenza: a comparative study of seasonal and pandemic influenza

Influenza epidemics lead to an increase in hospitalizations and deaths. Up to now the overall impact of attributable deaths due to seasonal and pandemic influenza viruses in Austria has not been investigated in detail. Therefore we compared the number and age distribution of influenza associated deaths during ten influenza epidemic seasons to those observed during the pandemic influenza A(H1N1)2009 season. A Poisson model, relating age and daily deaths to week of influenza season using national mortality and viral surveillance data adjusted for the confounding effect of co-circulating Respiratory Syncytial Virus was used. We estimated an average of 316 influenza associated deaths per seasonal influenza epidemic (1999/2000-2008/2009) and 264 for the pandemic influenza season 2009/2010 in the area of Vienna, Austria. Comparing the mortality data for seasonal and pandemic influenza viruses in different age groups revealed a statistically significant increase in mortality for pandemic A(H1N1)2009 influenza virus in the age groups below 34 years of age and a significant decrease in mortality in those above 55 years. Our data adjusted for co-circulating RSV confirm the different mortality pattern of seasonal and pandemic influenza A(H1N1)2009 virus in different age groups.     

Concurrent outbreaks of influenza A and influenza B

During the winter of 1982 concurrent outbreaks of influenza A and influenza B occurred. The epidemiology and clinical features of 151 cases referred during this time are described, and patients are discussed according to age and presenting clinical syndrome: croup was the commonest presentation in young children, a typical influenza syndrome predominated in young adults, while older patients were more likely to have lower respiratory tract infection. There was no significant difference between the clinical features of influenza A and influenza B. Unusual clinical features include rash, exudative tonsillitis and the need for myringotomy during the course of influenza.     

Protocol: Transmission and prevention of influenza in Hutterites: Zoonotic transmission of influenza A: swine & swine workers

Background  

Among swine, reassortment of influenza virus genes from birds, pigs, and humans could generate influenza viruses with pandemic potential. Humans with acute infection might also be a source of infection for swine production units. This article describes the study design and methods being used to assess influenza A transmission between swine workers and pigs. We hypothesize that transmission of swine influenza viruses to humans, transmission of human influenza viruses to swine, and reassortment of human and swine influenza A viruses is occurring. The project is part of a Team Grant; all Team Grant studies include active surveillance for influenza among Hutterite swine farmers in Alberta, Canada. This project also includes non-Hutterite swine farms that are experiencing swine respiratory illness.     

流感病毒变异与流行性感冒流行和预防

流感病毒不断变异是导致流行性感冒反复流行的基本因素。变异的表达是多方面的,但最经常并与流行关系最密切的是病毒抗原性变异．主要是指病毒包膜表面血凝索（H）的改变。抗原性变异分2类：即“抗原性漂移”和“抗原性转换”。另外毒力的变异在“抗原性漂移”过程中并不明显,但在“抗原性转换”时是至关重要的。病毒毒力可能是多基因综合的表现,在强毒株传播过程中基因节段核苷酸序列的改变,均可引起病毒原有的毒力下降。病毒“抗原性漂移”是在病毒亚型范围内的抗原性改变,它与人群感染后的免疫力有关,有明显的连续过程,一般较久的抗原性漂移,引发较大的流行性感冒流行,较小的抗原性漂移只能引起一些主要在儿童中的流行。但偶尔也可发现一些抗原性改变较大但传播力较差的病毒,不能成为流行的主流．短期内在人群中消失。经过流行后,人群对它的免疫水平很快提高,又促使病毒抗原性不断向前演变。     

Microbial adaptation and change: avian influenza

The evolution of influenza is a continuing process involving viral and host factors. The increasing frequency of emergence of the highly pathogenic H5N1, H7N3 and H7N7 influenza viruses and the panzootic spread of H9N2 influenza virus, all of which can be potentially transmitted to humans, are of great concern to both veterinary and human public health officials. The question is how soon the next pandemic will emerge. A convergence of factors, including the population densities of poultry, pigs and humans, are likely factors affecting the evolution of the virus. Highly concentrated poultry and pig farming, in conjunction with traditional live animal or 'wet' markets, provide optimal conditions for increased mutation, reassortment and recombination of influenza viruses. Strategies to reduce the evolution of influenza and the emergence of pandemics include the separation of species, increased biosecurity, the development of new vaccine strategies and better basic knowledge of the virus. More effective co-operation between scientists and veterinary and public health officials is required to achieve these goals.     

Swine influenza: epizootiological and serological studies

Studies of naturally occurring respiratory diseases in the midwestern parts of the USA showed that swine influenza is still prevalent and that mild forms as well as the classical forms of swine influenza occur. Outbreaks of respiratory disease of unknown etiology that are clinically similar to swine influenza were also found. On some farms, swine influenza occurred first in farrowing pens. It did not occur on some farms where the disease had occurred in previous years. This disappearance may have resulted from the elimination or hyperimmunization of breeder animals or from a change to the raising of swine obtained by caesarean section. Serological studies of swine with natural or experimental infections showed that antibody titres rose gradually for several months. This observation was corroborated in serological studies of sera obtained at the abattoir, which showed that older breeder swine had consistently higher titres than the younger market swine. These results cannot be explained by the lungworm hypothesis proposed by R. E. Shope for the survival and transmission of swine influenzavirus. It is suggested that breeder swine act as convalescent carriers and as the reservoirs of swine influenzavirus between epizootics.     

Does consecutive influenza vaccination reduce protection against influenza: A systematic review and meta-analysis

IntroductionVaccination against influenza on an annual basis is widely recommended, yet recent studies suggest consecutive vaccination may reduce vaccine effectiveness (VE).PurposeTo assess whether when examining the entirety of existing data consecutive influenza vaccination reduces VE compared to current season influenza vaccination.Data sourcesMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 26, 2017; citations of included studies.Study selectionRandomized, controlled trials (RCTs) and observational studies of children, adults and/or the elderly that reported laboratory-confirmed influenza infection over 2 or more consecutive influenza seasons were eligible.Data extractionData related to study characteristics, participant demographics, cases of influenza infection by vaccination group and risk of bias assessment was extracted in duplicate.Data synthesisFive RCTs involving 11,987 participants did not show a significant reduction in VE when participants vaccinated in two consecutive seasons (VE 71%, 95% CI 62–78%) were compared to those vaccinated in the current season (VE 58%, 95% CI 48–66%) (odds ratio [OR] 0.88, 95% CI 0.62–1.26, p = 0.49, I² = 39%). Twenty-eight observational studies involving 28,627 participants also did not show a reduction (VE for two consecutive seasons 41%, 95% CI 30–51% compared to VE for current season 47%, 95% CI 39–54%; OR 1.14, 95% CI 0.98–1.32, p = 0.09, I² = 63%). Results from subgroup analyses by influenza type/subtype, vaccine type, age, vaccine match and co-morbidity support these findings; however, dose–response results were inconsistent. Certainty in the evidence was assessed to be very low due to unexplained heterogeneity and imprecision.LimitationsThe inclusion of studies with relatively small sample sizes and low event rates contributed to the imprecision of summary VE and OR estimates, which were based on unadjusted data.ConclusionAvailable evidence does not support a reduction in VE with consecutive influenza vaccination, but the possibility of reduced effectiveness cannot be ruled out due to very low certainty in this evidence.Funding sourceCIHR Foundation Grant (PROSPERO: CRD42017059893).     

Avian and pandemic influenza: an overview

Influenza A/H5N1 (avian influenza) has now caused 258 human infections (as of November 13, 2006), with an approximate 50% mortality rate. Because the virus is novel in terms of antigenic type and causes infection and illness, and because humans have no pre-existing immunity, the conditions for a possible pandemic exist. Additionally, wild migratory birds appear to be spreading the virus across ever larger geographic areas, and newer clade 2 influenza A/H5N1 viruses have begun to emerge. The US Congressional Budget Office has formally modeled the likely consequences of pandemic influenza and estimates that up to 2 million of the US population might die, with up to 40% of all workers ill for as long as 3 or more weeks. This brief overview will review basic virologic, immunologic and epidemiologic information relevant to understanding and preparing for this threat. In particular, the role of avian influenza vaccines will be reviewed.     

Oculo-respiratory syndrome after influenza vaccination: trends over four influenza seasons

BACKGROUND: Oculo-respiratory syndrome (ORS) following influenza vaccination was identified in Canada in 2000. This report describes trends of ORS reported during four consecutive seasons 2000, 2001, 2002 and 2003 in the province of Quebec, Canada. METHODS: Data come from the vaccine-associated adverse event (VAAE) passive reporting system of the Province of Quebec. RESULTS: The rate of ORS reported per 100000 doses distributed declined from 46.6 in 2000 to 34.2, 20.6 and 9 in 2001, 2002 and 2003, respectively. There was no significant difference in rates for ORS between the two vaccines in use in Canada (Fluviral and Vaxigrip) both in 2001 and 2002. During the 4 years, incidence was highest in people aged 40-59 years and declined in older age groups. The clinical profile of ORS has remained remarkably stable over years. Overall, ocular, respiratory symptoms or facial edema were reported by 58%, 84% and 31% of patients, respectively, and 15% had symptoms including all three symptom categories. ORS lasted more than a week in 8-13% of the cases. CONCLUSION: ORS is an adverse event that occurred with both influenza vaccines used in Canada. Its frequency has declined substantially but is still present after 4 years. It constitutes a clinical entity distinct from anaphylactic allergy. Unlike anaphylaxis, ORS does not constitute an absolute contraindication to further doses.     

Concurrent outbreaks of influenza A and influenza B.

During the winter of 1982 concurrent outbreaks of influenza A and influenza B occurred. The epidemiology and clinical features of 151 cases referred during this time are described, and patients are discussed according to age and presenting clinical syndrome: croup was the commonest presentation in young children, a typical influenza syndrome predominated in young adults, while older patients were more likely to have lower respiratory tract infection. There was no significant difference between the clinical features of influenza A and influenza B. Unusual clinical features include rash, exudative tonsillitis and the need for myringotomy during the course of influenza.     

Live attenuated influenza virus vaccines: new options for the prevention of influenza

Live attenuated influenza virus (LAIV) vaccines present new possibilities for the prevention and control of influenza. Administered intranasally, LAIV vaccines offer a needle-free route of administration. These investigational vaccines have also been shown to be safe and effective in children and healthy working adults. A 2-year placebo-controlled trial among young children (1996-1997 and 1997-1998 influenza seasons) demonstrated that LAIV vaccine was associated with a 92% reduction in laboratory-confirmed cases of influenza. Vaccination also significantly reduced episodes of otitis media and antibiotic use. In a placebo-controlled trial among healthy working adults during the 1997-1998 season, LAIV vaccine significantly reduced episodes of febrile upper respiratory tract illness and illness-associated work loss, health-care use, and antibiotic use. Seventy percent of study participants self-administered the vaccine. An economic analysis of the benefits of LAIV vaccine in this population suggests that the break-even cost for LAIV vaccine and its administration for healthy working adults would be about $39. For both children and healthy adults, LAIV vaccine provided substantial protection during the 1997-1998 season when the predominant circulating virus, the A/Sydney variant, was not contained in the vaccine. Studies are still underway to evaluate the potential incremental benefits of LAIV vaccine in addition to inactivated vaccine in high-risk populations. LAIV vaccines will be an important addition to the armamentarium for fighting influenza.     

Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections

Mortality associated with influenza virus super-infections is frequently due to secondary bacterial complications. To date, super-infections with Streptococcus pyogenes have been studied less extensively than those associated with Streptococcus pneumoniae. This is significant because a vaccine for S. pyogenes is not clinically available, leaving vaccination against influenza virus as our only means for preventing these super-infections. In this study, we directly compared immunity induced by two types of influenza vaccine, either inactivated influenza virus (IIV) or live, attenuated influenza virus (LAIV), for the ability to prevent super-infections. Our data demonstrate that both IIV and LAIV vaccines induce similar levels of serum antibodies, and that LAIV alone induces IgA expression at mucosal surfaces. Upon super-infection, both vaccines have the ability to limit the induction of pro-inflammatory cytokines within the lung, including IFN-γ which has been shown to contribute to mortality in previous models of super-infection. Limiting expression of these pro-inflammatory cytokines within the lungs subsequently limits recruitment of macrophages and neutrophils to pulmonary surfaces, and ultimately protects both IIV- and LAIV-vaccinated mice from mortality. Despite their overall survival, both IIV- and LAIV-vaccinated mice demonstrated levels of bacteria within the lung tissue that are similar to those seen in unvaccinated mice. Thus, influenza virus:bacteria super-infections can be limited by vaccine-induced immunity against influenza virus, but the ability to prevent morbidity is not complete.