Efficacy of live attenuated influenza A/Scotland/74 (H3N2) virus vaccine against challenge with influenza A/Victoria/3/75 (H3N2) virus. Efficacy of sequential annual vaccination with inactivated influenza virus vaccine. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. Correlated studies of a recombinant influenza-virus vaccine. IV. Protection against naturally occurring influenza in military trainees. Immunogenicity of 1967 polyvalent and 1968 Hong Kong influenza vaccines. Is there a relationship between influenza vaccinations and risk of melanoma? A population-based case-control study. Field trial of live attenuated influenza A/B ("Alice"/R-75) vaccine. The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines. Effect of live attenuated, cold recombinant (CR) influenza virus vaccines on pulmonary function in healthy and asthmatic adults. Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers. Guillain-Barré syndrome in the United States, 1979-1980 and 1980-1981. Lack of an association with influenza vaccination. WRL 105 strain live attenuated influenza vaccine; comparison of one and two dose schedules. Ocular and respiratory symptoms attributable to inactivated split influenza vaccine: evidence from a controlled trial involving adults. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. Influenza A virus vaccines containing purified recombinant H3 hemagglutinin are well tolerated and induce protective immune responses in healthy adults. An evaluation of influenza immunization: influence of route of administration and vaccine strain. An assessment of oil adjuvant and aqueous influenza vaccines. I. Reactions to the vaccines. The effectiveness of vaccination against influenza in healthy, working adults. Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period. A placebo-controlled dose-response study of the reactogenicity and immunogenicity of a cold-adapted recombinant A/Victoria/3/75 (H3N2) live influenza virus candidate vaccine in healthy volunteers. [Effectiveness of an influenza vaccine in a working population in Colombia]. Reactogenicity and immunogenicity of parenteral monovalent influenza A/Victoria/3/75 (H3N2) virus vaccine in healthy adults. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: A randomized controlled trial. Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976--1977. Trivalent attenuated cold-adapted influenza virus vaccine: reduced viral shedding and serum antibody responses in susceptible adults. Safety and immunogenicity of a Proteosome -trivalent inactivated influenza vaccine, given nasally to healthy adults. Studies in man with a cold-recombinant live influenza B virus vaccine. Anthrax vaccination and risk of optic neuritis in the United States military, 1998-2003. The effect of vaccine on a closed epidemic of Hong Kong influenza. Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza vaccines administered intranasally to healthy adults. [Results of a study of the effectiveness of simultaneous immunization against influenza with live and inactivated vaccines (1980-1983)]. Efficacy of inactivated split-virus influenza vaccine against culture-confirmed influenza in healthy adults: a prospective, randomized, placebo-controlled trial. Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example. Influenza vaccination with live-attenuated and inactivated virus-vaccines during an outbreak of disease. Evaluation of an attenuated, cold-recombinant influenza B virus vaccine. [The trivalent polymer-subunit influenza vaccine Grippol studied in a controlled epidemiological trial (1)]. A graded-dose study of inactivated, surface antigen influenza B vaccine in volunteers: reactogenicity, antibody response and protection to challenge virus infection. Influenza vaccination and the risk of primary cardiac arrest. Clinical trial with "R-75" strain live, attenuated, serum inhibitor-resistant intranasal influenza B vaccine. Clinical trial of a subunit influenza vaccine. Responses to one or two doses of a deoxycholate subunit influenza vaccine in a primed population. An attenuated influenza virus vaccine: Reactogenicity, transmissibility, immunogenicity, and protective efficacy. Influenza immunization: field trial on a university campus. Do hospital employees benefit from the influenza vaccine? A placebo-controlled clinical trial. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. Impact of influenza vaccination on civilian aircrew illness and absenteeism. Clinical and serologic effects of live attenuated serum inhibitor-resistant influenza B vaccine in seronegative adults. Vaccinations and risk of central nervous system demyelinating diseases in adults.
For evaluation of heterologous protection by live attenuated influenza virus vaccine, 42 healthy volunteers with low titers of or no antibody to A/Scotland/74 (H3N2) and A/Victoria/3/75 (H3N2) influenza viruses were given live attenuated A/Scotland/74 (H3N2) virus vaccine or placebo by the intranasal route with no resultant vaccine-related illness. Seventeen of 21 vaccine recipients and none of 21 placebo recipients developed antibody conversion. Thirty-seven days after administration of vaccine or placebo, all subjects were challenged intranasally with wild-type A/Victoria/3/75 influenza virus. Five placebo recipients and no vaccine recipients developed moderately severe illness, whereas 10 vaccine recipients and three placebo recipients developed no illness (p less than 0.025). Although 16 of 21 vaccine recipients fulfilled criteria of infection with the challenge virus, shedding of virus was significantly less frequent, less prolonged, and of significantly lower magnitude than that in the placebo recipients. Thus, live attenuated influenza virus vaccine showed a significant protective effect against illness following challenge with heterologous wild-type virus. The protective effect and the negligible side effects of this vaccine merit consideration of its use in a large-scale field trial. Inactivated influenza virus vaccine efficacy after annual revaccination has been reported to be less than that after first vaccination in boarding school children. We prospectively examined the immunogenicity and efficacy of this vaccine in healthy 30- to 60-year-old volunteers in Houston, Texas, over two epidemic seasons (1983-1985) encompassing outbreaks due to influenza A (H3N2 and H1N1) and influenza B viruses. A placebo group that had never (or not in recent years) received inactivated influenza virus vaccine, a group that received the vaccine for the first time (first vac), and a group given two or more recent vaccinations (multivac) were evaluated in a double-blind fashion each year. Vaccination induced higher frequencies of rise in serum antibody titer to vaccine components in first vac than in multivac volunteers, but mean postvaccination titers were similar. Clinical and virologic evaluations of illnesses during both epidemics and of influenza infections diagnosed serologically over the epidemic seasons revealed no overall reduction in illness from that in the placebo group for either vaccine group; modest reductions in influenza infection-related illness that were significant only for the multivac group against A/H3N2-related illness (55%; p less than 0.04); reduction in moderate-to-severe lower respiratory and/or systemic illness due to influenza for multivac (73%, p less than 0.025) but not first vac (15%, p greater than 0.10) volunteers during the A/H3N2 epidemic; reduction in influenza virus shedding in the multivac (54%, p less than 0.05) but not the first vac (16%, p greater than 0.10) group when compared with the placebo group for both years; and overall 63-81% reductions in documented infections with each influenza virus for both vaccine groups with the exception of A/H1N1 for the first vac group (24%, p greater than 0.10) and type B for the multivac group (58%, p = 0.067). Vaccine efficacy was only modest in these studies, but in contrast to the earlier report in boarding school children, efficacy appeared to be somewhat greater after repeated annual vaccination than after first administration. A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacy of inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease. nan nan The aim of the present case-control study was to ascertain whether, in adults, yearly repeated anti-influenza vaccinations (AIV) enhance protection against cutaneous melanoma (CM), as do repeated febrile infections. Ninety-nine new cases of histologically confirmed CM and 104 healthy controls (matched to cases for sex, age, and skin colour) selected from the general population were examined in order to ascertain their skin type, the number of nevi on both arms, and the intensity of freckles on the face and the arms; in these subjects, a structured questionnaire was used to obtain information on age, sex, education, social class, exposure and susceptibility to sunlight, history of febrile infectious diseases, and vaccinations. The odds ratio (OR) and the 95% confidence interval (CI) were estimated by commonly used methods and by fitting models of logistic regression. The risk of CM was reduced in subjects with a history of febrile (temperature above 38.5 degrees C) infections in the 5 years prior to CM surgery (cases) or interview (controls), but was increased in those with voluntary exposure to sunlight in tropical countries. By holding the above factors constant at logistic regression analysis, it was found that a history of repeated AIV (3-5 times in the last 5 years) halved the risk (OR: 0.43; CI: 0.19-1.00; p < 0.05). With the variable 'nevi on arms' included, the protective influence of repeated AIVs was observed in a similar magnitude. The inverse relationship found between melanoma and influenza vaccinations is unlikely to have depended on a bias, even if based on replies in a questionnaire, because neither the interviewers nor the interviewers were informed in advance of the working hypothesis. The reactogenicity, immunogenicity and protection effecacy of a serum inhibitor-resistant live attenuated influenza A/B ("Alice"/R-75) vaccine was determined in a group of health young volunteers. The influenza A component was derived from A/England/42/72 (H3N2) strain, and the B component from B/Hong Kong/5/72 strain. Sixty-eight subjects had hemagglutination inhibition (HAI) antibody titers to influenza A hemagglutinin (HA) antigen of less than or equal to 1:8 ("low A" group) and 75 had similarly low antibody titers to B HA antigen ("low B" group). Two inocula given 14 days apart consisted of vaccine in two doses (VV); one dose of vaccine followed by placebo (VP); or two doses of placebo (PP). The reactogenicity of the vaccine was low, with approximately 25% of subjects in both the immunized and placebo categories having symptoms mainly of respiratory nature. The A component of the vaccine was immunogenic with 90.9% of the subjects in the low A group VV category showing seroconversion. By contrast, only 20% of VV subjects in the low B group seroconverted to B antigen. The vaccine afforded significant protection againndergone a slight antigenic drift. There was no difference in protection afforded either by one or two doses of the vaccine. Thus the overall protection efficacy following at least one dose of the vaccine was 80.0% (p = .01), and in the low A group subjects it was 85.5% (p = .01). The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk.
                Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey.
                We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12.
                There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza. The effects of intranasal inoculation with live attenuated, CR influenza virus vaccines on pulmonary function in healthy and asthmatic adults were evaluated in placebo-controlled, double-blind studies. In 46 healthy adult volunteers, there were no statistically significant alterations in pulmonary function as measured by spirometry and histamine bronchoprovocation tests in the first week following monovalent CR influenza virus vaccine [type A (H3N2, H1N1) and type B]. Among healthy adults with pre-inoculation PC20s less than 10 mg ml-1, 8/12 were infected following vaccination but no significant alterations occurred in histamine bronchoprovocation. In 11 asthmatic adults, no statistically significant alterations in pulmonary function, as measured by spirometry, were noted during the first 7 days postinoculation with bivalent CR influenza virus vaccine type A (H3N2 and H1N1). Postinoculation respiratory illnesses were more common in CR influenza virus vaccine recipients than placebo recipients, but they were mild, consisting of afebrile pharyngitis and transient rhinorrhea. Attenuated CR influenza virus vaccines do not appear to impair pulmonary function during the first week following immunization of healthy and asthmatic adults. In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce.
                To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers.
                A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs.
                Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased.
                Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings. An ongoing surveillance program was intensified during the 1979-1980 and the 1980-1981 influenza seasons to determine whether an increased risk of acquiring Guillain-Barré syndrome (GBS) within eight weeks after influenza vaccination existed for adults in the United States who received influenza vaccine, when compared with adult who had not been vaccinated recently. Five hundred twenty-eight cases of GBS with onset between Sept 1 and March 31, including seven following recent vaccination, were reported by participating neurologists in 1979-1980; 459 cases, including 12 following recent vaccination, were reported in 1980-1981. The relative risk of acquiring GBS following influenza vaccination--0.6 in 1979-1980 and 1.4 in 1980-1981--was not significantly different from 1.0 in either season. These results suggest that there was no increased risk of acquiring GBS associated with the influenza vaccines administered during these seasons and that the causative "trigger agent" in the A/New Jersey (swine) influenza vaccine administered in 1976 has not been present in subsequent influenza vaccine preparations. Haemagglutinating inhibiting antibody (HAI) responses were determined and clinical reactions recorded in 162 adult volunteers who received either 1 or 2 intranasal doses of 10(7-0) EID50 WRL 105 strain live influenza vaccine or placebo. After administration of a single dose of vaccine significant antibody responses were obtained in 69 (70%) of 98 volunteers with initial antibody titres of less than or equal to 1/20. Of the 70 volunteers who received a second dose of vaccine, 62 provided a further post-vaccination sample of serum, and only 3 (4-8%), who had not responded to the first dose of vaccine, produced a significant antibody response. Local, upper respiratory and constitutional symptoms were recorded more frequently after the administration of a first dose of vaccine than after placebo or a second dose of vaccine. The symptoms were of a minor nature except in one volunteer who, after the first dose of vaccine, developed influenzal symptoms followed by bronchitis. In 2000, an influenza vaccine was associated with unusual ocular and respiratory symptoms (known as "oculorespiratory syndrome" [ORS]) that possibly were due to numerous microaggregates of unsplit viruses present in the product. We assessed the potential for an improved vaccine formulation (for use in 2001-2002) to cause ORS and other symptoms in adults, using a double-blind, randomized, crossover study design. Symptoms were ascertained 24 h after 622 doses of vaccine and 626 doses of saline placebo were injected. The risk of ORS was 6.3% after vaccine injection and 3.4% after placebo injection, which yielded a significant vaccine-attributable risk of 2.9% (95% confidence interval, 0.6-5.2). ORS symptoms were mild. Significant differences in risk after injection of vaccine versus placebo existed for ocular soreness and/or itching (2.4%), coughing (1.6%), and hoarseness (1.2%). Vaccine-attributable general symptoms were infrequent. We conclude that certain mild oculorespiratory symptoms were triggered by an influenza vaccine that was otherwise minimally reactogenic and, hence, that such symptoms might be associated with influenza vaccines in general. Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.
                To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults.
                Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998.
                Thirteen centers across the United States.
                A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population.
                Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997.
                Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events.
                Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain.
                Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated. This study evaluated the safety, immunogenicity, and protective efficacy of vaccines containing purified recombinant uncleaved hemagglutinin (rHA0) from influenza A/Beijing/32/92 (H3N2) virus. In a randomized, double-blinded trial, 127 adult volunteers were immunized with 15 micrograms of rHA0, 15 micrograms of rHA0 plus alum, 90 micrograms of rHA0, licensed subvirion vaccine, or saline placebo. The rHA0 vaccines caused fewer local adverse reactions than did the commercial subvirion preparation. Neutralizing hemagglutinin-specific antibody responses to 15 micrograms of rHA0 were comparable to those elicited by licensed vaccine, not enhanced by the addition of alum, and significantly increased by raising the rHA0 dose from 15 to 90 micrograms. Compared with placebo recipients, rHA0-vaccinated subjects had significantly lower rates of influenza A (H3N2) virus infection and illness during the epidemic winter season. These results suggest that influenza vaccines containing purified rHA0 may offer an advantage over licensed preparations containing egg-grown antigens by inducing equivalent protective immune responses while being potentially less reactogenic. A field study was undertaken in Tampa, Fla., to assess the efficacy of subcutaneous and aerosol methods of administering vaccine, and to compare the protection afforded by bivalent (A2 and B) influenza virus vaccine and by A2/Hong Kong/68 virus vaccine. Further objectives of the study included a comparison of the effectiveness of single-dose and 2-dose immunization. Approximately 2100 volunteers received, in a double-blind manner, both an injection and an aerosol administration on 2 occasions 3 weeks apart. The results showed that aerosol administration gave a lower over-all protection rate, although the booster dose seemed to have a marked effect. The protection afforded by A2/Hong Kong/68 virus vaccine was considerably greater than that afforded by the bivalent vaccine, particularly when administration was subcutaneous. Results are also given on the occurrence of side-effects and on the correlation between cigarette smoking and the occurrence of influenza-like illness. nan Although influenza causes substantial morbidity and mortality in all age groups, current recommendations emphasize annual immunization for people at high risk for complications of influenza. We conducted a double-blind, placebo-controlled trial of vaccination against influenza in healthy, working adults.
                In the fall of 1994, we recruited working adults from 18 to 64 years of age from in and around the Minneapolis-St. Paul area and randomly assigned them to receive either influenza vaccine or placebo injections. The primary study outcomes included upper respiratory illnesses, absenteeism from work because of upper respiratory illnesses, and visits to physicians' offices for upper respiratory illnesses. The economic benefits of vaccination were analyzed by estimating the direct and indirect costs associated with immunization and with upper respiratory illnesses.
                We enrolled a total of 849 subjects. Baseline characteristics were similar in the two groups. During the follow-up period, consisting of the 1994-1995 influenza season (December 1, 1994, through March 31, 1995), those who received the vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo (105 vs. 140 episodes per 100 subjects, P < 0.001), 43 percent fewer days of sick leave from work due to upper respiratory illness (70 vs. 122 days per 100 subjects, P = 0.001), and 44 percent fewer visits to physicians' offices for upper respiratory illnesses (31 vs. 55 visits per 100 subjects, P = 0.004). The cost savings were estimated to be $46.85 per person vaccinated.
                Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults. Some reports have suggested that influenza virus vaccine is less effective in persons that have received prior annual vaccination(s) than in those receiving it for the first time. This issue was addressed by evaluating the efficacy of annual influenza vaccinations over a 5 year period in healthy adults employing commercially-available, inactivated whole-virus vaccine. Influenza vaccination had minimal effects on overall respiratory illnesses during epidemic periods. However, it reduced influenza virus shedding by an average of 38.8% and conferred protection against influenza virus infection during each epidemic. Some variation in infection rates were noted between vaccine groups given one or more than one annual immunization, and between years, but no consistent pattern of differences was noted in relation to number of successive years of vaccination. These results suggest that the current recommendation for annual influenza vaccination of persons at special risk of serious disease and complications is appropriate, but that continued efforts to improve the effectiveness of our prophylactic measures against influenza are needed. nan To determine if a vaccine against influenza significantly decreases episodes of acute upper respiratory infection (AURI) and work absenteeism caused by AURI, in healthy adult employees of a banking entity in the city of Medellín, Colombia.
                This was a double-blind randomized placebo-controlled study with 493 volunteers. The volunteers were randomly assigned to two groups, an experimental group and a control group, with 247 and 246 employees, respectively. The experimental group participants received a dose of 0.5 mL of an influenza vaccine containing surface antigens of the strains recommended by the World Health Organization for the 1996-1997 period, with subtypes A/Wuhan/359/95 (H3N2), A/Texas/36/91 (H1N1), and B/Beijing/184/93. An illness was considered an episode of AURI when a participant reported having a sore throat, fever, and a cough lasting more than 24 hours. Evaluations were made every 2 weeks over a 6-month period; the severity of the episodes was assessed in terms of lost workdays due to AURI (defined according to the ninth revision of the International Classification of Diseases, or ICD-9), through monthly evaluations of incapacitating work absences certified by the Colombian Social Security system, over the period of a year.
                Side effects associated with the vaccine were erythema (relative risk (RR) = 8.0; P = 0.02) and local edema (RR = 4.5; P = 0.03). The proportion of the annual cumulative incidence of episodes of AURI was 78.5% for the vaccinated persons and 91.5% for those in the placebo group, with a reduction of 14%, with values between 7% and 20% (RR = 0.86; 95% confidence interval (CI) = 0.80-0.93). The annual cumulative incidence of incapacitating AURI was 15.8% in those vaccinated, with a reduction of 31% in comparison to the placebo group (22.8%), with values between 0% and 52% (RR = 0.69; 95% CI = 0.48-1.0). These levels of protection, both against more mildly symptomatic forms of AURI and those causing lost workdays, increased significantly (between 62% and 89%) in the months of May and October, when outbreaks caused by the influenza virus were confirmed in Colombia.
                The results demonstrated that the influenza vaccination strategy decreased the AURI episodes as well as the number of work absences due to AURI in the healthy adult employees of a banking entity in the city of Medellín, Colombia. The impact that influenza has on this population group is small, and the effect of this vaccination measure is greater then the influenza virus is in circulation. Monovalent influenza A/Victoria/3/75 whole-virus vaccines prepared by Merck Sharp and Dohme (West Point, Pa.) and Merrell-National Laboratories (Cincinnati, Ohio) and split-virus vaccines prepared by Parke, Davis and Company (Detroit, Mich.) and Wyeth Laboratories (Philadelphia, Pa.) containing 200, 400, and 800 chick cell-agglutinating units per dose were compared with a placebo in double-blind trials in which 208 adults participated. Titers of hemagglutination-inhibiting antibody of greater than or equal to 1:20 were found in greater than 80% of the volunteers 21 days after vaccination. Seroconversion, defined as a fourfold or greater increase in antibody titer, occurred more frequently among seronegative volunteers than among seropositive volunteers. The geometric mean titers obtained with the whole-virus or split-virus vaccines were not significantly different. Reaction rates had no relation to seroconversion, nor did seronegative subjects have more reactions than seropositive subjects. Local reactions from all vaccines increased with increasing dose. Significantly more overall reactions, "bothersome" reactions, and febrile reactions occurred in the recipients of whole-virus vaccine. Of nine volunteers who reported temperatures of greater than 100 F, one had received split-virus vaccine, seven had received whole-virus vaccine, and one had received the placebo. Most systemic reactions were mild, and all were self-limited. Although the cost-effectiveness and cost-benefit of influenza vaccination are well established for persons aged 65 years or older, the benefits for healthy adults younger than 65 years are less clear.
                To evaluate the effectiveness and cost-benefit of influenza vaccine in preventing influenza-like illness (ILI) and reducing societal costs of ILI among healthy working adults.
                Double-blind, randomized, placebo-controlled trial conducted during 2 influenza seasons.
                Healthy adults aged 18 to 64 years and employed full-time by a US manufacturing company (for 1997-1998 season, n = 1184; for 1998-1999 season, n = 1191).
                For each season, participants were randomly assigned to receive either trivalent inactivated influenza vaccine (n = 595 in 1997-1998 and n = 587 in 1998-1999) or sterile saline injection (placebo; n = 589 in 1997-1998 and n = 604 in 1998-1999). Participants in 1997-1998 were rerandomized if they participated in 1998-1999.
                Influenza-like illnesses and associated physician visits and work absenteeism reported in biweekly questionnaires by all participants, and serologically confirmed influenza illness among 23% of participants in each year (n = 275 in 1997-1998; n = 278 in 1998-1999); societal cost of ILI per vaccinated vs unvaccinated person.
                For 1997-1998 and 1998-1999, respectively, 95% (1130/1184) and 99% (1178/1191) of participants had complete follow-up, and 23% in each year had serologic testing. In 1997-1998, when the vaccine virus differed from the predominant circulating viruses, vaccine efficacy against serologically confirmed influenza illness was 50% (P =.33). In this season, vaccination did not reduce ILI, physician visits, or lost workdays; the net societal cost was $65.59 per person compared with no vaccination. In 1998-1999, the vaccine and predominant circulating viruses were well matched. Vaccine efficacy was 86% (P =.001), and vaccination reduced ILI, physician visits, and lost workdays by 34%, 42%, and 32%, respectively. However, vaccination resulted in a net societal cost of $11.17 per person compared with no vaccination.
                Influenza vaccination of healthy working adults younger than 65 years can reduce the rates of ILI, lost workdays, and physician visits during years when the vaccine and circulating viruses are similar, but vaccination may not provide overall economic benefits in most years. JAMA. 2000;284:1655-1663. Because of an increase in the number of reports of Guillian-Barre syndrome (GBS) following A/New Jersey influenza vaccination, the National Influenza Immunization Program was suspended December 16, 1976 and nationwide surveillance for GBS was begun. This surveillance uncovered a total of 1098 patients with onset of GBS from October 1, 1976, to January 31, 1977, from all 50 states, District of Columbia, and Puerto Rico. A total of 532 patients had recently received an A/New Jersey influenza vaccination prior to their onset of GBS (vaccinated cases), and 15 patients received a vaccination after their onset of GBS. Five hundred forty-three patients had not been recently vaccinated with A/New Jersey influenza vaccine and the vaccination status for 8 was unknown. Epidemiologic evidence indicated that many cases of GBS were related to vaccination. When compared to the unvaccinated population, the vaccinated population had a significantly elevated attack rate in every adult age group. The estimated attributable risk of vaccine-related GBS in the adult population was just under one case per 100,000 vaccinations. The period of increased risk was concentrated primarily within the 5-week period after vaccination, although it lasted for approximately 9 or 10 weeks. Trivalent cold-adapted recombinant (CR) influenza virus vaccines containing types A (H1N1 and H3N2) and B viruses were evaluated in two double-blind, placebo-controlled trials. Susceptible adults were randomly assigned to receive the following vaccines by intranasal drops 1 month apart: two doses of trivalent vaccine, bivalent CR influenza A (Bi A) vaccine followed by monovalent B (Mono B) vaccine or vice versa, or two doses of placebo. All vaccines were well tolerated. Shedding of each of the three vaccine viruses was reduced after the first dose of trivalent vaccine compared with primary vaccination with Bi A or Mono B. Shedding was also reduced after second vaccinations, whether homologous (trivalent-trivalent) or heterologous (Bi A/Mono B or Mono B/Bi A). Reduced viral shedding was associated with reduced serum antibody responses. Thus, both simultaneous and sequential inoculations of susceptible adults with CR influenza vaccine viruses result in reduced viral shedding and serum antibody responses. We studied the safety and immunogenicity of a nasally administered vaccine comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently associated with outer membrane proteins of Neisseria meningitidis (Proteosome) in normal, healthy adults. In a randomized, double-blind trial participants (n = 78) were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or 45 microg of each of the three HA antigens, or two nasal doses containing 30 microg of each HA, separated by 2 weeks. The vaccine was generally well tolerated in all doses tested, and in a one or two-dose schedule. A shallow vaccine reactogenicity dose-response was seen. The most common local reaction was nasal congestion, which occurred in up to 48.3% of vaccine recipients in days 0-6 after vaccine but was mild and self-limiting; this reaction was not significantly more common among active vaccine recipients than placebo recipients. Mild to moderate headache was the most commonly reported systemic reactogenicity complaint in all treatment groups, and was the only solicited complaint to increase significantly in frequency after a second active dose. No severe systemic reactions occurred. A positive and statistically significant antibody response was observed, in serum and in nasal secretions, to increasing dose for all three antigens. Serum HAI titre responses and nasal secretory IgA immune responses were elicited against all three antigens. Further testing of this nasal influenza vaccine is warranted to determine its safety and immunogenicity in these populations and its efficacy in the prevention of clinical illness. A cold recombinant live influenza B virus vaccine was tested in man. In comparison to a placebo, reactogenicity attributable to virus infection was slight or moderate. No revertant viruses were shed, and there was no evidence of transmission to the placebo group who were housed in close contact with the vaccinees. Serological responses to initial inoculation were moderate; 60% of vaccinees showing twofold increases in serum hemagglutination inhibition (HAI) titers gave a geometric mean titer (GMT) of 1:13. Three weeks after the first vaccination, both the vaccine and the placebo group were revaccinated with homologous live virus vaccine. The group previously given vaccine was resistant to reinfection as judged from clinical reactions and virus shedding and the GMT increased only slightly to 1:16.3. In contrast, the former placebo group responded; mild symptoms were seen, the majority shed viruses and 50% showed twofold increases in serum HAI titers to a geometric mean titer of 1:17.4. Numerous case reports have suggested a possible association between optic neuritis and receipt of several different vaccines. The most frequently identified vaccines associated with optic neuritis in the literature are influenza and hepatitis B, and a report describing 2 US military cases suggests an association with the currently used anthrax vaccine (anthrax vaccine adsorbed).
                To test the hypothesis that optic neuritis may be associated with anthrax, smallpox, hepatitis B, and influenza vaccines.
                We conducted a matched case-control study among US military personnel from January 1, 1998, through December 31, 2003, using the Defense Medical Surveillance System. Statistical associations between vaccine exposures and optic neuritis within 6-, 12-, and 18-week study intervals were estimated through multivariable conditional logistic regression analyses.
                A total of 1131 cases of optic neuritis and 3393 controls were matched by sex, military component, and deployment status.
                No statistically significant associations between optic neuritis and anthrax vaccine were observed for any of the 3 study intervals: 6-week interval (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.74-1.87), 12-week interval (OR, 0.92; 95% CI, 0.63-0.35), and 18-week interval (OR, 0.81; 95% CI, 0.58-1.14). Furthermore, no difference in optic neuritis risk was detected when comparing those who received no dose, 1 dose, and 2 doses of anthrax vaccine. Similarly, no statistically significant associations were observed between optic neuritis and smallpox, hepatitis B, or influenza vaccines within any of the study intervals. No vaccine to vaccine interactions were statistically significant.
                The results from this vaccine postmarketing surveillance investigation suggest that there is no association between optic neuritis and receipt of anthrax, smallpox, hepatitis B, or influenza vaccinations in the US military, whether these vaccines are administered alone or in combination. The negative findings presented here are important to the continuing discussions regarding the safety of these vaccines. nan Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection. Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies, but are poor inducers of mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice. We conducted an open-label safety study followed by an observer-blind, randomized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo. Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a serum antibody response was slightly lower. The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine. Both vaccines gave more frequent responses than seen in placebo recipients, indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses. A comparative evaluation of immunological and epidemiological effectiveness of commercial live and killed vaccine preparations used simultaneously or separately was first carried out in simultaneous field trials of various methods of influenza vaccine prevention in a human population of 10,449 subjects. The advantage of simultaneous immunization was confirmed by immunological parameters and protective effect in the period of influenza A epidemic of 1983. The correlation of immunological and epidemiological effectiveness of influenza vaccines in joint or separate administration is discussed. A new trivalent inactivated split-virus influenza vaccine (TIV) was recently introduced in the United States. We assessed the efficacy of TIV against culture-confirmed influenza A and/or B.
                In this double-blind trial conducted from September 2006 to May 2007 in the Czech Republic and Finland, participants aged 18-64 years were randomized to receive 1 dose of TIV (n = 5103) or placebo (n = 2549). Influenza-like illnesses (ILI) (defined as at least 1 systemic symptom [fever {oral temperature, > or = 37.8 degrees C} and/or myalgia] and at least 1 respiratory symptom [cough and/or sore throat]) were identified by both active (biweekly phone contact) and passive surveillance. Nasal and throat swab specimens were collected for viral culture.
                The attack rate for culture-confirmed ILI was 3.2% in the placebo group, with most strains identified as influenza A (all except 1 were H3N2) matching the vaccine strain. There were 6 cases of influenza B, all of which were of a different lineage (Yamagata) than the vaccine strain. Vaccine efficacy against culture-confirmed influenza A and/or B due to strains antigenically matched to the vaccine was 66.9% (95% confidence interval [CI], 51.9%-77.4%; P < .001) and to any strain was 61.6% (95% CI, 46.0%-72.8%; P < .001).
                TIV is efficacious against culture-confirmed influenza in healthy adults.
                ClinicalTrials.gov identifier: NCT00363870. Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.
                6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was > or = 45%. Cases of influenza like illness (defined as fever (oral temperature > or =37.8 degrees C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.
                TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).
                Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.
                Clinical trial registery: NCT00197223. Immunization procedures with live attenuated and inactivated vaccines were carried out on a group of young recruits at the beginning of an outbreak of infection due to an A/Victoria/3/75-related virus strain, which occurred in February 1977 in a military camp. A retrospective investigation on protection from clinical influenza was then performed in order to investigate whether immunization with live virus vaccines, administered at the beginning of an epidemic, could provide early protection from the disease. In the course of the two weeks following vaccination, laboratory-confirmed clinical influenza cases occurred in 4 subjects among the 110 volunteers of the control group which received placebo, and in 8, 7 and 4 subjects respectively of the 3 groups of about 125 individuals, each of which received one of the following vaccine preparations: (a), live attenuated A/Victoria/3/75 influenza virus oral vaccine, grown on chick embryo kidney culture; (b), live attenuated nasal vaccine, a recombinant of A/Puerto Rico/8/34 with A/Victoria/3/75 virus; and (c), inactivated A/Victoria/3/75 virus intramuscular vaccine. These data do not support the hypothesis that, during an epidemic of infection, early protection from clinical influenza can be achieved through immunization with live attenuated or inactivated influenza virus vaccines, in spite of the high immunizing capability of the vaccine preparations. A live, attenuated influenza B virus vaccine was evaluated in a group of students. The virus, cold-recombinant (CR) 7, was produced by recombining the attenuated cold-adapted parent, B/Ann Arbor/1/66, with a wild strain, B/Hong Kong/8/73. In ferrets, the wild strain produced histopathologic lesions in the lungs, whereas the CR strain and the attenuated parent did not. A total of 306 individuals was inoculated intranasally with either the CR virus or a placebo. After inoculation, only one symptom was significantly more common in the vaccinees than in the control subjects. That symptom, sore throat, occurred briefly in 26% of the vaccine recipients and in 10.5% of the placebo recipients. An outbreak of influenza B occurred three months after vaccination. When serologic infection rates in the two groups were compared, it was found that the vaccine had been significantly effective (P less than 0.01) in preventing infection. nan One hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 micrograms of HA or saline alone in a 0.5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response. The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 micrograms HA and least for those given 5 micrograms HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 micrograms HA, 22 (96%) showed a fourfold rise in antibody titre and all volunteers had antibody titres of greater than 40 following immunization: for volunteers given 5 micrograms HA the g.m.t. increased from 16.6 to 86.1; and for those given 10 and 20 micrograms HA the response was intermediate. Following challenge, the lowest incidence of infection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50% protection titre of serum HI antibody was estimated as 15 to 20. Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes, and cardiovascular mortality increases abruptly during influenza epidemics, with little evidence of a lag period. In a population-based case-control study, the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest (PCA), a major contributor to cardiovascular mortality in the community. Cases of PCA (n = 342) without prior heart disease or life-threatening comorbidity that occurred in King County, Washington, were identified from paramedic incident reports from October 1988 to July 1994. Demographically similar controls (n = 549) were identified from the community by using random digit dialing. Spouses of subjects were interviewed to assess treatment with influenza vaccine during the previous year and other risk factors. After adjustment for demographic, clinical, and behavioral risk factors, influenza vaccination was associated with a reduced risk of PCA (odds ratio = 0.51, 95 percent confidence interval: 0.33, 0.79). The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of influenza vaccination and total mortality, further studies are needed to determine whether the observed association reflects protection or selection. The "R-75" strain live, attenuated, serum inhibitor-resistant influenza B vaccine was administered intranasally by drops in two doses 14 days apart to 21 volunteers. Each vaccinee was paired with a close associate (roommate or workmate) who similarly received two doses of a placebo solution. Although about 50% of both vaccine and placebo recipients complained of symptoms after dosage, the severity of symptoms was greater in vaccine recipients. Fourfold serum hemagglutination-inhibiting antibody titer rises occurred in 38% of vaccine recipients, and four vaccines had fourfold titer rises of nasal hemagglutination-inhibiting antibody. Vaccine virus was isolated from three asymptomatic vaccine recipients. There was no virological or serological evidence of the vaccine virus spreading to placebo recipients. A double-blind field trial was performed comparing a subunit influenza vaccine (A/Victoria/75 and B/Hongkong/73) with placebo. A good protection against influenza was induced by the vaccine. On the basis of serological determinations (enzyme immunoassay, EIA) the incidences of influenza A and B infections were reduced within a period from 3 weeks up to 5 months after the vaccination by 88 and 68%, respectively. Three weeks after the vaccination 79% of the vaccines had acquired protective serum antibody levels (greater than or equal to 32 x 10(2) by EIA) against influenza A and 62% against influenza B, while in the control subjects protective antibody levels were measured in frequencies from 4 to 13% in subsequent serum samples. With a few exceptions antibody levels were still present in 5-month samples. Side effects were recorded within the first 3 days following the vaccination. Some minor symptoms like redness and tenderness at the vaccination site and muscle ache were reported more frequently by the vaccines than by the controls, but no more harmful systemic reactions. A trial with a trivalent influenza subunit vaccine prepared with sodium deoxycholate was carried out in 88 volunteers between May and November 1981. Each haemagglutinin antigen was present at 7 micrograms per dose. Fourfold or greater haemagglutination inhibition antibody (HI) responses to the H1N1 virus A/Brazil/11/78 occurred in 70% of volunteers following a single dose. For the H3N2 virus A/Bangkok/1/79 and B/Singapore/222/79 these figures were 52 and 11%, respectively. No increase in the antibody titre was noted to any of the antigens following a second vaccination dose. Antibody levels remained relatively constant six months after vaccination. A response to B/Singapore/222/79, comparable with the HI response for the influenza A antigens, was noted when serum titres were estimated by a plaque reduction procedure. No neuraminidase inhibition antibody could be detected in response to either A/Brazil/11/78 or A/Bangkok/1/79. No reactions specifically attributable to the vaccine occurred after either injection. A lower HI response to A/Brazil/11/78 was noted in volunteers 52 years of age and older, who also showed less evidence of earlier priming to this virus. Levels of nasal wash neutralizing antibodies to A/Brazil/11/78 were proportional to those detected in sera by HI tests, but were present in smaller amounts. nan nan Although current guidelines target hospital employees who contact high-risk patients as a high priority for influenza immunization, there are few data to support or refute this recommendation. Therefore, the authors enrolled 179 hospital employees in a randomized double-blind placebo-controlled clinical trial during the 1985-1986 influenza season. Influenza immunization was performed without serious adverse reactions and there was no increase in absenteeism attributable to the vaccination. Among those who developed clinical influenza, there was a trend toward fewer days of illness in the vaccinated group compared with the placebo group (6.0 vs. 8.0, p = 0.07). There were no statistically significant differences between subjects receiving influenza vaccine and those receiving the placebo when comparing incidences of influenza-like illness, severities of illness, and sick absenteeism. Influenza immunization of hospital employees was performed at minimal cost and risk but provided little benefit, most likely because of an unexpected drift of the prevalent influenza strain away from the vaccine type. After the introduction of an inactivated intranasal influenza vaccine that was used only in Switzerland, 46 cases of Bell's palsy were reported.
                We conducted a matched case-control study and a case-series analysis. All primary care physicians, ear, nose, and throat specialists, and neurologists in German-speaking regions of Switzerland were requested to identify cases of Bell's palsy diagnosed in adults between October 1, 2000, and April 30, 2001. Each physician was invited to select three control patients for each patient with Bell's palsy, with matching according to age, date of the clinic visit, and physician. Vaccination information was provided by the physicians.
                A total of 773 patients with Bell's palsy were identified. Of the 412 (53.3 percent) who could be evaluated, 250 (60.7 percent) were enrolled and matched with 722 control patients; the other 162 patients had no controls. In the case-control study, we found that 68 patients with Bell's palsy (27.2 percent) and 8 controls (1.1 percent) had received the intranasal vaccine (P<0.001). In contrast to parenteral vaccines, the intranasal vaccine significantly increased the risk of Bell's palsy (adjusted odds ratio, 84.0; 95 percent confidence interval, 20.1 to 351.9). Even according to conservative assumptions, the relative risk of Bell's palsy was estimated to be 19 times the risk in the controls, corresponding to 13 excess cases per 10,000 vaccinees within 1 to 91 days after vaccination. In the case-series analysis, the period of highest risk was 31 to 60 days after vaccination.
                This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell's palsy. This vaccine is no longer in clinical use.
                Copyright 2004 Massachusetts Medical Society Approximately 10% of the general population worldwide acquires influenza infection every year. Airline crews run a particularly high risk of contracting influenza and influenza-like viruses because they come in contact with hundreds of potentially infected individuals every day. Respiratory diseases are the most frequent cause of absenteeism among flight crews in airline companies. Several studies have shown the efficacy of influenza vaccination in the workplace of healthy, working adults leading to increased productivity and lower absenteeism. We conducted a double blind, randomized, placebo-controlled study on flight crews of an airline company in order to determine the safety and efficacy of a trivalent inactivated influenza vaccine in reducing illness and absences from work.
                The 813 healthy members of a Brazilian airline company were randomly assigned to receive injections of either an influenza vaccine or a placebo, with a follow-up period of 7 mo after vaccination. Primary outcomes included influenza-like illness episodes and absenteeism from work due to such episodes.
                Demographic characteristics were similar in the two groups. No significant side-effects occurred in either group. Compared to the placebo group, individuals receiving the vaccine showed 39.5% fewer episodes of flu-like illness (p < 0.001) and 26% fewer days of work lost (p = 0.03). The vaccinated group developed 33% fewer episodes of any severe flu-like illness (p < 0.01).
                The data indicates that influenza vaccination is safe in airline flight crews and may produce health-related benefits including reduced absenteeism. The clinical effects, nasal and serum antibody responses, and virus excretion of a live attenuated serum inhibitor-resistant influenza B virus vaccine, R75, was evaluated in 43 seronegative healthy adults by a random double-blind study. Symptom responses were minimal and were not significantly different between vaccine and placebo groups. No fevers, abnormalities in physical examination or laboratory testing developed during 4 weeks of observation. Among vaccinees, 10 (48%) developed serum hemagglutination-inhibition (HI) antibodies, 16 (76%) developed serum neutralization (N) antibodies and 4 (19%) developed nasal N antibodies. The GMT responses from study day 0 to day 28 were 4.0 to 10.4 for serum HI, 1.8 to 9.8 for serum N, and 1.0 to 1.4 for nasal N. There were no significant titer changes in the placebo group. No virus excretion was detected. Although there are some questions concerning the relationship of antibody levels to protection, the low antibody responses in this study are an indication that R75 is not sufficiently immunogenic. Several case reports of the onset or exacerbation of multiple sclerosis or other demyelinating conditions shortly after vaccination have suggested that vaccines may increase the risk of demyelinating diseases.
                To evaluate the association between vaccination and onset of multiple sclerosis or optic neuritis.
                Case-control study involving cases of multiple sclerosis or optic neuritis among adults 18 to 49 years of age. Data on vaccinations and other risk factors were obtained from computerized and paper medical records and from telephone interviews.
                Three health maintenance organizations.
                Four hundred forty case subjects and 950 control subjects matched on health maintenance organization, sex, and date of birth.
                None.
                Onset of first symptoms of demyelinating disease at any time after vaccination and during specified intervals after vaccination (<1 year, 1-5 years, and >5 years).
                Cases and controls had similar vaccination histories. The odds ratios (95% confidence intervals), adjusted for potential confounding variables, of the associations between ever having been vaccinated and risk of demyelinating disease (multiple sclerosis and optic neuritis combined) were 0.9 (0.6-1.5) for hepatitis B vaccine; 0.6 (0.4-0.8) for tetanus vaccination; 0.8 (0.6-1.2) for influenza vaccine; 0.8 (0.5-1.5) for measles, mumps, rubella vaccine; 0.9 (0.5-1.4) for measles vaccine; and 0.7 (0.4-1.0) for rubella vaccine. The results were similar when multiple sclerosis and optic neuritis were analyzed separately. There was no increased risk according to timing of vaccination.
                Vaccination against hepatitis B, influenza, tetanus, measles, or rubella is not associated with an increased risk of multiple sclerosis or optic neuritis.
Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.

WARNING:
This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.