Evaluation of the effectiveness of influenza trivalent polymer subunit vaccine "Grippol"

Influenza polymer-subunit vaccine "Grippol", made up of the sterile conjugate of surface proteins of influenza viruses, groups A and B, with polyoxidonium (copolymer), was obtained at the State Scientific Centre of Research Institute of Immunology. As the result of our investigations, the coefficient of prophylactic effectiveness of vaccine "Grippol" was found to be 71%; in the presence of the 50% immune stratum in the group the coefficient of antiepidemic protection was found to be 66.4%. At the same time, cases of influenza and acute respiratory diseases were shown to take a milder form in persons immunized with vaccine "Grippol" than in the group of nonimmunized subjects. The results of this investigation did not show any side effects caused by the vaccine.     

Field trial with a new type of influenza subunit vaccine (author's transl)

In a field trial a new influenza subunit vaccine was tested in parallel with a vaccine prepared from the whole virus. The subunit vaccine essentially contained only the proteins of the viral envelope, haemagglutinin and neuraminidase, which had been selectively solubilized by treatment with cetyl trimethylammonium bromide. Both vaccines contained 700 IU of strain A/Port Chalmers/73 in 0.5 ml. They were given to volunteers by the subcutaneous route with and without the addition of Al (OH)3 as adjuvant. Blood samples were taken on days 0, 28 and 90. Development of antibodies was assayed in the haemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) test. All vaccines exhibited a very good immunogenic effect as judged from the number of volunteers with at least a four-fold rise in antibodies in the HI-test and those reaching titres that are considered to be sufficiently high for protection against disease. The best results were obtained with the aqueous subunit vaccine. All four vaccines also stimulated the formation of neuraminidase-inhibiting antibodies. The vaccines were well tolerated by the volunteers. The incidence of minor local reactions such as redness, swelling and pain varied according to the vaccine used, as shown on statistical evaluation. The aqueous subunit vaccine clearly proved to be superior in this respect.     

Clinical effectiveness of influenza vaccination in Manitoba

OBJECTIVE: To assess the clinical effectiveness of influenza vaccination in preventing influenza-associated hospitalization and death. DESIGN: Case-control study. SETTING AND PATIENTS: Noninstitutionalized persons aged 45 years or older living in Manitoba, on December 1, 1982, and December 1, 1985. METHODS: Linked records of the Manitoba population registry, hospital-discharge abstracts, physician claims for ambulatory-patient visits and influenza vaccination, and vital statistics were used. A matched-set analysis estimated the clinical effectiveness of influenza vaccination in preventing hospital admissions and deaths from influenza-associated conditions during influenza A (H3N2) outbreak periods in 1982 to 1983 (12 weeks) and 1985 to 1986 (10 weeks). The analysis adjusted for hospital discharge and ambulatory care for high-risk conditions within the previous 15 months and 3 months, respectively. RESULTS: Influenza vaccination prevented 32% to 39% of hospital admissions with pneumonia and influenza and 15% to 34% of admissions with all respiratory conditions. Vaccination was 43% to 65% effective in preventing hospital deaths with these conditions (all listed diagnoses) and 27% to 30% effective in preventing deaths from all causes. CONCLUSION: Influenza vaccination has substantial clinical effectiveness in preventing hospital admission and death from influenza-associated conditions in noninstitutionalized individuals.     

Effect of influenza vaccine on bronchoprovocation testing in normal subjects

A study of 55 nonasthmatic patients was undertaken to determine if recent influenza vaccination is a justifiable exclusionary criteria for bronchoprovocation testing. Healthy subjects without history of asthma and with negative methacholine challenge tests were given an intramuscular injection of killed influenza vaccine. Methacholine challenge testing was repeated 24 h later. While a statistically significant decline in FEV1 at 188 methacholine dose units was demonstrated (p < 0.018), this was not clinically significant; none of the 55 subjects converted a negative test to positive. We conclude that recent influenza vaccination is not a sufficient exclusionary criterion for methacholine challenge testing. Positive results in a patient recently vaccinated would still indicate asthma in the correct clinical setting.     

Therapeutic effectiveness of bonafton and rimantadine in influenza

The therapeutic effectiveness of bonaphthone and rimantadine was studied by treatment of 439 patients with influenza between 18 and 21 years of age (bonaphthone 94, controls 105, rimantadine 120, controls 120). No therapeutic effectiveness of bonaphthone was established in the study. When rimantadine was given to the patients from the 1st day of the disease, shorter intervals of normalization of the temperature, disappearance of toxicity and catarrhal symptoms were observed than in patients treated with symptomatic drugs. During the period of rimantadine therapy the rate of findings the influenza antigen in smears from the nasal mucosa was lower, but after termination of the course of treatment the antigen was found twice as frequently as in the control group. With the positive therapeutic effect in patients treated with rimantadine, the diagnostic rise of antibody in this group was observed in a lower per cent of cases than in the control group (13 and 20%, respectively). The results of immunofluorescent and serological studies indicate a possible virus reproduction-inhibiting effect of rimantadine. This, however, requires further study. On the basis of the above observations rimantadine may be recommended for treatment of patients with influenza.     

Estimation of vaccine effectiveness using the screening method

We report the clinical, radiologic, and postmortem findings in two patients with paroxysmal nocturnal hemoglobinuria (PNH) who developed cerebral venous thromboses (CVTs). In contrast with those in most published cases, our patients did not have focal neurologic signs. Antemortem diagnosis of CVT had been made by MR cerebral venograms. We conclude that (1) PNH should be considered in any patient with stroke associated with iron deficiency anemia, hemolysis, hemoglobinuria, or hemosiderinuria; (2) PNH should be in the differential diagnosis of CVT; (3) the latter could present without focal neurologic signs; and (4) MR cerebral venography may be a reliable diagnostic alternative to cerebral angiography when CVT is suspected.     

Safety of influenza vaccine in heart transplant recipients

BACKGROUND: Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. METHODS: During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. RESULTS: Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. CONCLUSIONS: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.     

Adverse effects associated with influenza vaccine in pediatrics

To investigate mechanisms of capillary network remodeling, we developed a serum-free angiogenesis in vitro system in three-dimensional fibrin matrices which allows the study of directional growth of endothelial sprouts, anastomosis, and remodeling ('pruning') of the primitive plexus toward more elaborated capillary trees. To follow the movements of living endothelial cells by inverse-fluorescence microscopy, we cocultured unlabeled endothelial cells with endothelial cells labeled with the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). We show that elongation and retraction of neighboring capillary sprouts occurs simultaneously, resembling a tug-of-war by which endothelial cells are withdrawn from shortening sprouts to become incorporated in other sprouts nearby. For the first time, we directly demonstrate the long-suspected parallel sliding movement of endothelial cells. We show that cell migration persists within immature capillaries even after sprouts have merged to continuous capillary loops, leading to overlapping growth of opposing sprout tips. As a novel concept of capillary remodeling, we distinguish two types of endothelial cell migration: sprouting and guided migration. Sprouting is the de novo invasion of a matrix by endothelial cells, and guided migration is the locomotion of cells along preexistent capillary-like structures. We show that guided migration leads to remodeling of immature capillary networks and to the retraction of sprouts. We describe a method for quantification of sprouting versus guided migration in DiI-mosaic-labeled capillary networks, and we present evidence that endothelial cell-derived basic fibroblast growth factor serves as a chemotactic signal for other cells to migrate along a preestablished capillary-like structure.     

Recent progress in live influenza vaccine development]

As live influenza vaccine, cold-adapted influenza virus vaccines (ca vaccine) have been extensively investigated in both the U.S and Russia. In Russia it has been licensed since 1988 and it is going to be licensed in the U.S. within a year or two. In general, the ca vaccine is more effective in seronegative population than the inactivated vaccine. In seropositive adult population, both are equally effective. In the elderly, inactivated vaccine is better than the live vaccine. In Japan, clinical trials were also conducted with the American ca vaccines. Although the efficacy was confirmed in limited locations, the vaccine could not be evaluated from the point of license approval because big epidemic did not occur during the studies.     

Effect of prednisone on response to influenza virus vaccine in asthmatic children

OBJECTIVE: To evaluate the immunogenicity of the influenza virus vaccine in children receiving short-course (a burst) prednisone therapy for acute asthmatic exacerbations. DESIGN: Prospective cohort study. SETTING: Outpatient pediatric clinic of a military medical center. PATIENTS: Children aged 6 months to 18 years requiring the 1996 influenza virus vaccine were eligible for the study. A total of 58 children were enrolled initially. The control group included 37 asthmatic children requiring less than 900 microg/d of inhaled prednisone and their siblings. The prednisone group included 21 children vaccinated at the beginning of a course of prednisone prescribed to treat an asthma exacerbation. Thirty-one control subjects (84%) and 19 patients in the prednisone group (90%) completed the study. Dropout was due to failure to come in for the postvaccination serum sampling. INTERVENTIONS: All study patients underwent immunization with the 1996-1997 trivalent subvirion influenza virus vaccine (FluShield; Wyeth Laboratories Inc, Marietta, Pa) containing 15-microg hemagglutinin antigens each of A/Texas/36/91 (H1N1) (A/H1), A/Wuhan/359/95 (H3N2)(A/H3), and B/Beijing/184/93 (B). The prednisone cohort received a burst of oral prednisone therapy (2 mg/kg per day for 5 days). MAIN OUTCOME MEASURES: To assess the immunogenicity of the vaccine between both groups, at least a 4-fold rise in titer and end titers of at least 1:40 to each of the 3 antigens were compared. Mean changes in geometric titers to the 3 antigens were also compared. RESULTS: Proportion of patients in each group with at least a 4-fold rise in titer to each of the influenza antigens was as follows: for A/H3N3 antigen, 15 patients (79%) in the prednisone group vs 22 controls (71%) (P = .74); for A/ H1N1 antigen, 16 patients in the prednisone group (84%) vs 20 controls (64%) (P = .20); and for B antigen, 7 patients in the prednisone group (37%) vs 8 controls (26%) (P = .53). Proportion of patients in each group with an end titer of at least 1:40 to each of the antigens was as follows: for A/ H3N2 antigen, 18 patients in the prednisone group (95%) vs 28 controls (90%) (P = .69); for A/H1N1 antigen, 17 patients in the prednisone group (89%) vs 26 controls (84%) (P = .99); and for B antigen, 7 patients in the prednisone group (37%) vs 13 controls (42%) (P = .99). There were also no significant differences between groups in the mean changes in geometric titers to any of the 3 antigens. CONCLUSIONS: Prednisone bursts did not diminish the response of asthmatic children to the 1996 influenza virus vaccine, compared with controls. Children can be effectively vaccinated against influenza virus while they are receiving prednisone therapy bursts for asthmatic exacerbations.     

Characteristic of humoral response of elderly to inactivated influenza vaccine

Eighty persons immunized with inactivated influenza vaccine in 1990-1991 epidemic season were examined. Serological tests: hemagglutination inhibition (HI), lectin neuraminidase (LN) and Western blot were performed with serum specimens taken before and 3-4 weeks after vaccination. Distribution of anti-influenza antibodies in the subclass was also examined. The results revealed humoral response to vaccine strains of influenza virus and also to strains caused infections in the past.     

Intranasal immunization with attenuated live influenza vaccine in asthma

Attenuated live intranasal influenza vaccine ("Alice") was given to 20 asthmatics and 9 control subjects. Pulmonary function were performed before and after, with emphasis on tests of small airways function (using flow volume curves with air and a helium-oxygen mixture). In subjects with a low influenza A antibody titer, there was a 4-fold rise in titer to the vaccine, whereas those subjects with a high titer showed no rise. There were no significant changes in pulmonary function in any parameters measured, and no significant symptoms were reported. We have concluded from this study that "Alice" appears safe for use in asthma and was capable of producing an antibody titer rise in persons with low titers.     

Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults

The adjuvanted influenza vaccine FLUAD is composed of subunit influenza antigens combined with the MF59-adjuvant emulsion. The vaccine was developed primarily for use in elderly populations, but non-elderly individuals might also benefit. To evaluate this hypothesis, 301 healthy adults were assigned randomly to receive two intramuscular injections of either FLUAD (150 subjects) or a non-adjuvanted vaccine, Fluzone (151 subjects), in two trials conducted at a 1-year interval. Injections consisted of 15 micrograms per 0.5 ml dose. Vaccine composition was A/Texas/36/91 (H1N1), A/Johannesburg/33/94 (H3N2), and B/Harbin/7/94 for the first injection and A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2), and B/Harbin/7/94 for the second injection. Immunogenicity was evaluated at 28 and 180 days post-immunization. FLUAD was generally well tolerated in healthy adults when compared with Fluzone. FLUAD was associated with increased pain at the injection site after immunization. A statistically significant increase in the incidence of injection-site warmth, chills, myalgia, and analgesic/antipyretic use occurred in the FLUAD group after the first injection but not after the second injection. In both groups, most of these local and systemic reactions were classified as mild. FLUAD was more immunogenic than Fluzone following both injections. After the first injection, statistically significant differences were found in the percentage of subjects with four-fold rises in hemagglutinin inhibition (HI) titers at 28 days post-immunization for the B antigen. After the second injection, the FLUAD group had significantly higher HI titers, a significantly higher percentage with a four-fold increase in titer, and a significantly greater percentage of subjects with titers >/=160 for the H3N2 antigen at 28 days. Only minor immunogenicity differences between the two groups were seen at 180 days. Compared with Fluzone, FLUAD was associated with increased immunogenicity and mild post-immunization reactions in healthy adults. The magnitude of increased immunogenicity in healthy adults was less than that seen in elderly populations.     

提高质量管理小组活动有效性探讨

介绍了唐钢通过发挥领导作用、坚持培训教育、健全管理体系、缩短质量管理小组活动周期、着眼实际保证成果质量、有效地实施“三结合”,提高了质量管理小组活动有效性的工作探讨。     

An investigation of the prevalence of psychological morbidity in burn-injured patients

Research on the psychological impact of burn injuries has concentrated on major burns, while small burns have been largely neglected. In a prospective study, 45 patients with burn injuries ranging from 1 per cent or less up to 40 per cent total body surface area were assessed using semi-structured interviews within 2 weeks of sustaining the burn, and followed-up at approximately 3 months postburn to investigate the prevalence of mental health problems. The prevalence of clinically significant levels of anxiety, intrusions and avoidance remained similar at 2 weeks and 3 months postburn, however, the prevalence of depression and Post Traumatic Stress Disorder (PTSD) increased 6- and 4-times, respectively, by 3 months. Patients with small burn injuries of 1 per cent or less also experienced clinically significant levels of psychological difficulties postburn. The implications for the identification of patients at risk of future psychological morbidity are discussed.     

Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma

BACKGROUND: Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds. METHODS: We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%). FINDINGS: Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees. INTERPRETATION: Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination.