Influenza

The `weekly returns' system for the reporting of infectious and communicable diseases to the Birmingham Research Unit of the Royal College of General Practitioners is described. A detailed analysis of the influenza returns for the winter epidemic of 1975/76 is presented and compared with similar data from the previous ten-year period.

This analysis allows the following generalizations to be made which can, to a limited extent, be used as broad guidelines for predictions.

In any week in which a rate of 20 or more reports per 100,000 population is followed by a week in which there is a trebling of the rate, a major epidemic is imminent in which a peak rate of 500 cases per 100,000 population can be expected within three to four weeks.

In any week other than a week referred to previously in which a rate of 30 cases or more per 100,000 population is followed by a doubling of the rate, a moderate epidemic is imminent and peak rates in the range 150 to 500 per 100,000 population will be reached within three to four weeks.

The earlier in the critical period just before and just after Christmas that either of these changes are noted, the earlier and larger the peak is likely to be. Where neither of these thresholds is crossed, the peak rate for reported influenza is unlikely to exceed 150 cases per 100,000 people.

     

Liposomal Influenza Vaccine

black triangle This trivalent liposomal influenza vaccine consists of purified influenza haemagglutinin inserted into a membrane of phosphatidylcholine and phosphatidylethanolamine. It contains 15microg of haemagglutinin per viral strain per dose. black triangle The vaccine is immunogenic in the elderly, in younger adults and in children and adolescents with or without cystic fibrosis. black triangle Seroconversion rates were significantly higher with the liposomal vaccine than with a subunit vaccine for 3 of 3 and 2 of 3 strains in 2 published studies. Seroconversion occurred in a significantly greater number of participants receiving the liposomal vaccine than in those receiving a whole virus vaccine for all 3 strains in 1 study. black triangle Seroprotection rates were significantly better with the liposomal vaccine than with a subunit vaccine for 2 of 3 and 1 of 3 strains in 2 trials, and greater than with a whole virus vaccine for 2 of 3 strains in 1 trial. black triangle In a study in children with cystic fibrosis, a single dose of the liposomal vaccine was reported to have greater immunogenicity than 2 half doses (statistical analysis not performed). black triangle Local adverse reactions such as pain at the injection site, local induration, redness and swelling are transient and usually mild. black triangle Liposomal influenza vaccine did not induce a mean antiphospholipid antibody response in elderly volunteers.     

Adjuvanted Influenza Vaccine

black triangle Adjuvanted influenza vaccine is composed of 2 type A and 1 type B inactivated influenza subunits combined with an oil-and-water emulsion (MF59). Each dose contains 15microg haemagglutinin per strain. black triangle Adjuvanted influenza vaccine was immunogenic in elderly vaccinees and in younger adults after 1 to 3 consecutive annual injections. black triangle According to studies available to date, the adjuvanted vaccine was more immunogenic than the nonadjuvanted subunit or split virus vaccines and the virosomal vaccine for 1 to 3 of the 3 strains tested per injection. black triangle The immunogenic effect generally persisted for longer after the adjuvanted vaccine than the nonadjuvanted subunit vaccine in elderly recipients. black triangle The adjuvanted vaccine also appeared to be more effective than the nonadjuvanted subunit vaccine against antigenically different heterovariant strains in elderly vaccinees. black triangle The 28-day seroprotection rate in 4 studies was significantly greater after the adjuvanted vaccine for 1 or 2 of the 3 strains tested compared with the nonadjuvanted subunit vaccine and the virosomal vaccine and for 1 of 3 strains compared with the split virus vaccine. black triangle The incidence of systemic adverse events was generally low. Local reactions such as pain, erythema and induration occurred more frequently with the adjuvanted than the 2 nonadjuvanted or the virosomal vaccines; however, these were mild and transient.     

Influenza vaccine immunology

Studying the spread of influenza in human populations and protection by influenza vaccines provides important insights into immunity against influenza. The 2009 H1N1 pandemic has taught the most recent lessons. Neutralizing and receptor-blocking antibodies against hemagglutinin are the primary means of protection from the spread of pandemic and seasonal strains. Anti-neuraminidase antibodies seem to play a secondary role. More broadly cross-reactive forms of immunity may lessen disease severity but are insufficient to prevent epidemic spread. Priming by prior exposure to related influenza strains through infection or immunization permits rapid, potent antibody responses to immunization. Priming is of greater importance to the design of immunization strategies than the immunologically fascinating phenomenon of dominant recall responses to previously encountered strains (original antigenic sin). Comparisons between non-adjuvanted inactivated vaccines and live attenuated vaccines demonstrate that both can protect, with some advantage of live attenuated vaccines in children and some advantage of inactivated vaccines in those with multiple prior exposures to influenza antigens. The addition of oil-in-water emulsion adjuvants to inactivated vaccines provides enhanced functional antibody titers, greater breadth of antibody cross-reactivity, and antigen dose sparing. The MF59 adjuvant broadens the distribution of B-cell epitopes recognized on HA and NA following immunization.     

流感大流行期间疫苗免疫方案的传染病模型

目的模拟流感大流行期间疫苗免疫方案控制疫情的效果,对比两种疫苗免疫方案的效果差异,为制订应急方案提供数据参考。方法基于传染病的自然规律,在传统SEIR模型的基础上建立对人群免疫的传染病模型,采用感染率（AR）作为判断指标,对全人群免疫和部分人群免疫（排除康复人群）两种免疫方案进行效果对比。结果对于R0在2左右的流感大流行,感染者均表现临床症状的情况下,随着疫苗延迟时间（TL）和完成时间（DV）的缩短,感染率下降。当控制目标设定为将感染率控制在50%以下时,采用全人群免疫方案的最大TL和DV组合为40和30 d;采用部分人群免疫方案的最大TL和DV组合为两者均为40 d,或两种方案的TL和DV最大组合均为30和80 d。如果不能在短期内开展和完成疫苗计划（TL在30 d内,DV为20 d内）,则部分人群免疫方案可以更快地降低感染率。结论为最大程度地减少大流行期间的生命损失,将感染率控制在50%以下,防病重点应为尽早开展和完成疫苗计划,如果TL在30 d以上,则部分人群的免疫方案更有利于疫情的控制。