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Canada Communicable Disease Report
Volume 27 ACS-4 1 August 2001 An Advisory Committee Statement (ACS) STATEMENT ON INFLUENZA VACCINATION FOR THE 2001-2002 SEASONAdobe Downloadable Document (262 KB) PreambleThe National Advisory Committee on Immunization (NACI) provides Health Canada with ongoing and timely medical, scientific, and public-health advice relating to immunization. Health Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge, and is disseminating this document for information purposes. Persons administering or using the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian licensed manufacturer(s) of the vaccine(s). Manufacturer(s) have only sought approval of the vaccine(s) and provided evidence as to its safety and efficacy when used in accordance with the product monographs. IntroductionThe antigenic components of the influenza vaccine have been updated for the 2001-2002 season. The present statement contains new information on influenza epidemiology and control among children, national coverage rates for influenza vaccination, and dosage regimens for prophylactic amantadine. The section entitled "Administration of Influenza Vaccine" contains an interim report of vaccine-associated adverse events, primarily consisting of an oculo-respiratory syndrome (ORS), observed during the 2000-2001 influenza immunization season. Studies regarding ORS are ongoing, and further results will be published in CCDR as they become available. In Canada, two available measures can reduce the impact of influenza: immunoprophylaxis with inactivated (killed-virus) vaccine and chemoprophylaxis or therapy with influenza-specific antiviral drugs (amantadine and neuraminidase inhibitors). At the time of writing of this statement, neuraminidase inhibitors have been licensed for therapy but not for chemoprophylaxis against influenza in Canada. Vaccination of persons at high risk each year before the influenza season is currently the most effective measure for reducing the impact of influenza. Influenza A viruses are classified into subtypes on the basis of two surface antigens: hemagglutinin (H) and neuraminidase (N). Three subtypes of hemagglutinin (H1, H2, and H3) and two subtypes of neuraminidase (N1 and N2) are recognized among influenza A viruses that have caused widespread human disease. Immunity to these antigens - especially to the hemagglutinin - reduces the likelihood of infection and lessens the severity of disease if infection occurs. Infection with a virus of one subtype confers little, or no, protection against viruses of other subtypes. Furthermore, over time, antigenic variation (antigenic drift) within a subtype may be so significant that infection, or vaccination, with one strain may not confer immunity to distantly related strains of the same subtype. Although influenza B viruses have shown more antigenic stability than influenza A viruses, antigenic variation does occur. For these reasons, major epidemics of respiratory disease caused by new variants of influenza continue to occur. During the 2000-2001 influenza season, lower than usual activity was reported for all national indicators of influenza activity, including the rate of influenza-like illness (ILI), the percentage of laboratory-confirmed cases of influenza and provincial/territorial influenza activity levels. Increased laboratory-confirmed influenza activity began in the West (Yukon, prairie provinces and British Columbia) in mid-December, peaking in early to mid-January, followed by the Atlantic provinces peaking in early February, with Ontario and Quebec peaking in early to mid-March. There was no prominent peak of activity in Canada and the season reflected a mix of early and prolonged influenza B circulation and late influenza A circulation. Between 27 August 2000 and 21 April 2001, the Centre for Infectious Disease Prevention and Control (CIDPC) received reports on 46,336 laboratory tests for influenza; 4,154 (9%) tests were confirmed positive for influenza; of those, 32% (1,324) were identified as influenza A and 68% (2,830) as influenza B. As of 10 May 2001, the National Microbiology Laboratory (NML), CIDPC, has characterized 507 isolates: 48% (241) were A/New Caledonia/20/99 (H1N1)-like; 1% (5) were A/Johannesburg/82/96 (H1N1)-like; < 1% (2) were A/Panama/2007/99 (H3N2)-like; 51 % (258) were B/Yamanashi/166/98-like; and < 1% (1) was B/Beijing/243/97, which is a B/Victoria/2/87-like virus. The single case of B/Beijing/243/97-like virus, likely imported into Canada, was isolated in Quebec in March 2001. There has been a relative increase in influenza B activity in Canada this season as well as a drop in influenza A activity, compared to last year. During the 1999-2000 season < 1% (66) of detected isolates were identified as influenza B while 99.1% (6,961) were influenza A, compared to 68% influenza B and 32% influenza A detected during the 2000-2001 season. Furthermore, as compared to last season when 89% (437) of the characterized influenza A isolates were identified as H3N2 (all were A/Sydney/5/97(H3N2)-like viruses) and only 9% (46) were identified as H1N1 (all were A/New Caledonia/20/99(H1N1)-like viruses), only 1% (2) of this season's characterized influenza A isolates were identified as H3N2 and 99% (246) were identified as H1N1. Up to 21 April 2001, 9% (258/2,830) of the influenza B isolates were antigenically characterized as B/Yamanashi/166/98. However, it has been noted that 89% of the influenza B isolates characterized by the United States (U.S.) Centers for Disease Control and Prevention were antigenically more closely related to B/Sichuan/379/99, a reference strain which has been found to cross react with B/Yamanashi/166/98. Preliminary results of genetic analyses completed at the NML indicated that this antigenic change was found in a percentage of the Canadian influenza B isolates. It should also be noted that B/Sichuan/379/99 virus exhibits cross-reactivity with the 2000-2001 vaccine strain. The vaccine strains in the 2000-2001 influenza vaccine either matched or produced high titres of antibody that cross-reacted with all of the A and B strains characterized by the NML during the 2000-2001 season. Worldwide, influenza activity in the Northern hemisphere was initially reported during the 3rd week of November 2000 and peaked in early to mid-February 2001. Most influenza activity was attributable to influenza A (H1N1), which co-circulated with influenza B. Influenza A (H3N2) viruses were only sporadically isolated. Many countries reported outbreaks of both influenza A (H1N1) and influenza B; however, no countries reported any outbreaks of influenza A (H3N2). In most countries the greatest impact was in children and young adults. Since October 2000, 52 countries report laboratory-confirmed influenza A to the World Health Organization (WHO), while only 34 countries report influenza B. Both subtypes of influenza A (H3N2 and H1N1) and influenza B were detected on six continents (Africa, North America, South America, Asia, Europe, and Oceania). Influenza A (H1N1) appeared to be the predominant circulating virus and subtype. Of the H1N1 isolates, A/new Caledonia/20/99 (H1N1) was the predominant circulating strain world-wide, including Canada and the U.S.. Two other H1N1 strains were detected in Europe and North America: A/Johannesburg/82/96 and A/Bayern/7/95. Less commonly detected were the H3N2 strains, the most common of which was A/Panama/2007/99, an A/Moscow/10/99(H3N2)-like virus. A/Panama/2007/99 and/or A/Moscow/10/99 were detected in Europe, Asia and North and South America, including Canada and the U.S. Five strains of influenza B were detected: B/Beijing/184/93 and B/Yamanashi/166/98, B/Sichuan/379/99, B/Harbin/07/94 and B/Shangdong/7/97. B/Sichuan/379/99 was the more common strain detected, isolated in 17 countries on three continents, including Canada and the U.S. The antigenic characteristics of current and emerging influenza virus strains provide the basis for selecting the strains included in each year's vaccine. As suggested by WHO, NACI recommends that the trivalent vaccine for the 2001-2002 season in the Northern hemisphere contain an A/Moscow/10/99 (H3N2)-like virus, an A/New Caledonia/20/99 (H1N1)-like virus, and a B/Sichuan/379/99-like virus. Vaccine products may use antigenically equivalent strains because of their growth properties. The influenza strains that will be used in licensed Canadian vaccines will be announced soon in an upcoming issue of CCDR. Immunization against influenza must be given annually. The recommended time for influenza immunization is the period from October to mid-November. However, decisions regarding the exact timing of vaccination of ambulatory and institutionalized individuals must be made based on local epidemiology, recognition of the need to use patient contacts with health care providers as opportune moments for immunization, and programmatic issues. Further advice regarding the timing of influenza vaccination programs may be obtained through consultation with local medical officers of health. Health care workers should use every opportunity to give vaccine to any individual at risk who has not been immunized during the current season, even after influenza activity has been documented in the community. Update on Influenza Epidemiology and Control Among ChildrenRecent American studies have demonstrated rates of hospitalization for cardiopulmonary disease during influenza season, among children <= 4 years of age, ranging from 100/100,000 population for those without high-risk conditions, to 500/100,000 for those with high-risk conditions(1-5). Within this age group, the hospitalization rates were greatest among children <= 1 year of age, both for those with and without conditions that put them at risk for influenza complications; these rates are similar to those previously reported among adults >= 65 years of age. The studies were not designed to demonstrate whether influenza viral infection was a cause or cofactor in precipitating hospitalization among these children. Potential confounding variables include the cocirculation of other respiratory pathogens, including respiratory syncytial virus, during influenza season. A small recently published U.S. randomized controlled trial of influenza vaccination was conducted in 1996-1997 among day care children 24 to 60 months of age(6). Previously unimmunized children received two doses of vaccine. Vaccine efficacy was 31% to 45% in preventing serologically proven influenza A and B virus infection. There were no reductions in respiratory or febrile respiratory illnesses among vaccinated children. The authors postulated that the low vaccine efficacy demonstrated in this study may have been attributable to reduced efficacy of the 1996-1997 vaccine. Febrile respiratory illness was significantly diminished among influenza-unvaccinated household contacts of influenza-vaccinated day care children, compared to the household contacts of control children(7). The authors suggest that influenza vaccine may reduce transmission of virus from infected vaccinated children to susceptible contacts. Studies are ongoing regarding the benefits, risks, costs and programmatic issues associated with the routine immunization of healthy young children, as well as adults(5). [See "Immunization of healthy persons"]. Update on National Coverage Rates for Influenza VaccinationIn 1993 a national consensus conference on influenza set a target rate of 70% for influenza immunization coverage for persons >= 65 years of age, as well as persons with medical conditions who are at high-risk for influenza related complications(8). In January 2001 Health Canada commissioned a random-digit dialling telephone survey in order to evaluate progress toward this national target. The survey interviewed 3,501 non-institutionalized Canadian residents >= 18 years of age, from all provinces and territories. The recently published results(9) indicate that among those interviewed who were >= 65 years of age, 69% received influenza vaccination during the 2000-2001 influenza season. However, only 38% of those 18 to 64 years of age who have high-risk medical conditions(9,10), and 55% of health care workers who have close contact with patients, were immunized during this season. Intensified efforts are required to improve influenza immunization coverage rates in these high-risk groups. Recommendations for the prevention and control of influenza during the 2001-2002 influenza season follow. Recommended recipientsCurrent influenza vaccines licensed in Canada are immunogenic, safe and associated with minimal side effects [see "Adverse reactions" and "Contraindications and precautions"]. Influenza vaccine may be administered to any healthy child, adolescent or adult for whom contraindications are not present. To reduce the morbidity and mortality associated with influenza and the impact of illness in our communities, immunization programs should focus on those at high-risk for influenza-related complications, those capable of transmitting influenza to individuals at high- risk for complications, and those who provide essential community services. However, significant morbidity and societal costs are also associated with seasonal inter-pandemic influenza illness and its complications occurring in healthy children and adults. For this reason, healthy adults and their children who wish to protect themselves from influenza should be encouraged to receive the vaccine [see "Immunization of healthy persons"]. People at high risk for influenza-related complications
People capable of transmitting influenza to those at high risk for influenza-related complications People who are potentially capable of transmitting influenza to those at high risk should receive annual vaccination, regardless of whether the high-risk person(s) is immunized.
People who provide essential community services Vaccination may be considered for these individuals in order to minimize the disruption of routine activities in epidemics. Employers and their employees should consider yearly influenza immunization for healthy working adults as this has been shown to decrease work absenteeism from respiratory and other illnesses(32-35). Further comments regarding recommended recipients
In the U.S. the American Academy of Family Physicians (AAFP) and the Advisory Committee on Immunization Practices (ACIP) have recommended lowering the age of universal influenza vaccination of adults to 50 years of age(5,43). The primary rationale is that many persons 50 to 64 years of age have high-risk conditions such as diabetes mellitus, or heart disease, yet the influenza immunization rate among U.S. adults in this age group who have high-risk chronic medical conditions is low(5). The low immunization rate is caused by persons being unaware they have a high-risk condition, lack of health care access, or failure of HCWs to deliver immunization. Age-based influenza guidelines may be more successful in reaching individuals with medical conditions that put them at higher risk of influenza complications, compared to previous guidelines based on recognition of the specific high-risk conditions. The cost-benefit ratio of this change in U.S. guidelines has not been fully assessed. At the present time NACI suggests that programmatic decisions in Canada regarding how to access and immunize those listed under "Recommended Recipients" are best made by agencies responsible for the planning and implementation of such programs.
Administration of Influenza VaccineDosage schedule The recommended dosage schedule and type of influenza vaccine are presented
in Table 1. Split-virus vaccines are available in
Canada. Previously unvaccinated children < 9 years of age require two doses
of the split-virus influenza vaccine, with an interval of 4 weeks. The
second dose of influenza vaccine is not needed if the child has received one
or more doses of vaccine during a previous influenza season.
In infants < 6 months of age, influenza vaccine is less immunogenic than in infants and children 6 to 18 months of age. Therefore, immunization with currently available influenza vaccines is not recommended for infants < 6 months of age. Intramuscular administration is preferred. The deltoid muscle is the recommended site in adults and older children, the anterolateral thigh in infants and young children. Interim Report on Adverse Events observed during the 2000-2001 Influenza Vaccination Season Overview Between 1 September, 2000 and 21 March, 2001, Health Canada received a total of 2,450 reports of influenza vaccine-associated adverse events, of which 1,735 (71%) described ocular or respiratory symptoms. Of these reports, 960 (39%) were classified as meeting a newly-created case definition for what was described as "oculo-respiratory syndrome (ORS)". ORS was defined as the presence of red eyes, respiratory symptoms (cough, sore throat, difficulty breathing, wheezing, and chest tightness), facial edema, or a combination of these symptoms developing within 2 to 24 hours of influenza immunization and resolving within 48 hours(50). Most of the adverse events were reported following a call for enhanced surveillance of adverse events following influenza vaccination, issued in mid-October 2000. Seventy-five percent of reported cases occurred in adults between 30 and 59 years of age and 76% were females. There were nine cases reported in children < 9 years of age. The syndrome is generally mild and self-limiting, although 24% consulted a health care provider and 11 cases (1%) required hospitalization. Approximately 75% of adverse events consisting of oculo-respiratory symptoms resolved spontaneously within 48 hours. There were no deaths reported in association with ORS. Of 960 cases, information on the type of vaccine used was available in 937 cases; however, in 23 cases the type of vaccine used was not known. Nine hundred and twenty-five (96%) cases of ORS occurred following receipt of Fluviral S/F® produced by BioChem Pharma. All but one of the distributed lots of Fluviral S/F® have been implicated, however the lot that was not implicated was distributed in very small quantities. Twelve cases occurred following receipt of Fluzone® or Vaxigrip®, both produced by Aventis Pasteur Limited. Close to 12.2 million doses of influenza vaccine were distributed in Canada during the 2000-2001 season: 8.4 million doses of Aventis Pasteur products and 3.8 million of BioChem Pharma product. Although the number of these reported adverse events is higher than in the past, conjunctivitis or respiratory symptoms following influenza immunization have been previously reported in Canada, in the U.S. and in Europe (Dr. David Scheifele, Vaccine Evaluation Centre, University of British Columbia, Vancouver, British Columbia: personal communication, 2001)(Dr. Robert Pless, Centers for Disease Control and Prevention, Atlanta, Georgia: personal communication, 2001). Upon review, some of these cases fit the current definition of ORS (Dr. David Scheifele, Vaccine Evaluation Centre, University of British Columbia, Vancouver, British Columbia: personal communication, 2001), although vaccine-associated oculo-respiratory symptoms were not recognized as a syndrome in the past. The 2000-2001 influenza season in Canada was characterized by enhanced promotion of vaccination, particularly in Ontario. Intensified surveillance for adverse events was initiated when ORS was recognized, and appropriate steps were taken to inform patients and the public. These factors must be considered when comparing the number of adverse events reported in past influenza seasons. During the 2000-2001 influenza season a similar increase in the number of reported oculo-respiratory vaccine-associated adverse events was not observed in the U.S.(Dr. Robert Pless, Centers for Disease Control and Prevention, Atlanta, Georgia: personal communication, 2001). Epidemiologic Studies In British Columbia (B.C.) several epidemiologic studies were conducted during the 2000-2001 influenza season to determine the risk of developing oculo-respiratory symptoms after receipt of Fluviral S/F® (Dr. David Scheifele, Vaccine Evaluation Centre, University of British Columbia, Vancouver, British Columbia: personal communication, 2001)(Dr. Danuta Skowronski, B.C. Centre for Disease Control, Vancouver, British Columbia: personal communication, 2001). Two retrospective cohort studies were conducted among 181 and 411 individuals respectively, comparing the incidence of symptoms in vaccinees and non-vaccinees, and one study compared the incidence of symptoms among 305 vaccinees following influenza immunization this season as compared to previous influenza immunization seasons. From 1% to 12% of recipients of Fluviral S/F® developed ORS (red eyes, respiratory symptoms, facial edema, or a combination of these) within 24 hours of receipt of influenza vaccine and lasting < 48 hours, compared to 0% to 8% of non-vaccinees. Vaccinees were significantly more likely to develop ocular symptoms this year as compared to previous years (Dr. Danuta Skowronski, B.C. Centre for Disease Control, Vancouver, British Columbia: personal communication, 2001). A retrospective cohort study was also conducted in British Columbia among influenza vaccinated diabetic children and their siblings (Dr. David Scheifele, Vaccine Evaluation Centre, University of British Columbia, Vancouver, British Columbia: personal communication, 2001). Among the 656 children who received Fluviral S/F®, ORS symptoms were reported in 12%; the rate did not differ between those with, or without, diabetes. First-time vaccinees were 2.8 times more likely to experience ORS. Symptoms of muscle and joint pain were strongly associated with ORS. Two retrospective cohort surveys of vaccinated subjects in Quebec suggested that 3% of Fluviral S/F® recipients developed red eyes or respiratory symptoms within 24 hours of immunization. Female sex and being between 40 and 59 years of age were considered significant risk factors for developing the syndrome(51). Product-related investigations Product-related investigations performed in response to reports of ORS included a comparison of ingredients, inactivation tests, reverse phase and size-exclusion high pressure liquid chromatography, polyacrylamide gel electrophoresis, and transmission electron microscopy. All three vaccines used the same influenza strains and seed stocks. The vaccines were completely inactivated. All products contained thimerosal. BioChem Pharma (Fluviral S/F®) used deoxycholate (DOC) to split the virus, whereas Aventis Pasteur used Triton X-100. Electron microscopy revealed a higher proportion of unsplit (whole) virus and a higher proportion of aggregated virus particles in Fluviral S/F® as compared to the Aventis vaccines (Dr. Laszlo Palkonyay, Bureau of Biologics and Radiopharmaceuticals, Health Canada, Ottawa, Ontario: personal communication, 2001). The ORS syndrome was not previously reported in association with whole virus vaccines, which were in use in Canada until 1997. Clinical studies In the first phase of a clinical study, skin testing is being conducted in 160 volunteers: 40 who were immunized with Fluviral S/F® and who reacted, 40 who were immunized with Fluviral S/F® but were not affected, 40 who were immunized with an Aventis Pasteur product and 40 non-immunized individuals. The skin testing study aims to quantify the hypersensitivity response to the three vaccine products, the monovalent whole products and the monovalent split products. Results will be made available when the study is completed (Dr. Danuta Skowronski, B.C. Centre for Disease Control, Vancouver, British Columbia: personal communication, 2001). Another clinical trial is being planned for August 2001, in order to assess the safety of the 2001-02 influenza vaccines prior to licensure (Dr. David Scheifele, Vaccine Evaluation Centre, University of British Columbia, Vancouver, British Columbia: personal communication, 2001). Outcomes of primary interest will be the incidence rate of ORS in vaccinees, the relative risk of the syndrome in vaccinees as compared to non-vaccinees, and the risk of reoccurrence of the symptoms in subjects who experienced ORS in 2000-2001. Pathophysiologic mechanism The pathophysiologic mechanism that underlies ORS remains unknown. A number of hypotheses have been raised. ORS may occur due to T cell-mediated hypersensitivity to a component in the Fluviral S/F® vaccine (a peptide or other component), perhaps through an accelerated type IV hypersensitivity reaction. Alternatively, ORS may be caused by a non-specific immune response such as interferon release in response to viral components. The preliminary reports from a B.C. pediatric study of an association between ORS and first-time vaccinees, as well as an association with symptoms of muscle and joint pain, support a possible role for interferon in this syndrome (Dr. David Scheifele, Vaccine Evaluation Centre, University of British Columbia, Vancouver, British Columbia: personal communication, 2001)(Dr. Danuta Skowronski, B.C. Centre for Disease Control, Vancouver, British Columbia: personal communication, 2001). Therapeutic interferon use may cause flu-like symptoms (fever, headache, malaise), as well as red eyes, cough, pharyngitis, shortness of breath and other symptoms within a few hours of injection (Dr. Danuta Skowronski, B.C. Centre for Disease Control, Vancouver, British Columbia: personal communication, 2001). A Canadian study from 1989-1990, when whole virus influenza vaccines were still licensed, showed a higher rate of malaise, myalgia or arthralgia (or both) in adults receiving whole virus compared to split virus vaccine(52). The mechanism of these adverse effects may be related to interferon release. Conclusions regarding adverse events noted during the 2000-2001 Vaccination Season
Recommendations arising from the 2000-2001 Vaccination Season
Other adverse reactions described in previous CCDR statements Influenza vaccination cannot cause influenza because the vaccine does not contain live virus. Soreness at the injection site lasting <= 2 days is common, but rarely interferes with normal activities. Fever, malaise, and myalgia may occur within 6 to 12 hours after vaccination and last 1 to 2 days, especially in young adults who have received the whole-virus vaccine and those receiving vaccine for the first time. Prophylactic acetaminophen may decrease the frequency of some side effects in adults(53). Healthy adults receiving the split-virus vaccine showed no increase in the frequency of fever or other systemic symptoms compared to those receiving placebo. In children 2 to 12 years of age, fever and local reactions are no more frequent after administration of split-virus vaccine than after placebo injections. In those < 24 months of age, fever occurs more often, but is seldom severe. Allergic responses are rare and are probably a consequence of hypersensitivity to some vaccine component, most likely residual egg protein, which is present in minute quantities. Rare cases of systemic vasculitis have been reported to occur in individuals within 2 weeks of influenza vaccination(54). Influenza antigens have not been identified in circulating immune complexes or in vessel walls, and a causal relationship has not been proven. Guillain-Barré syndrome (GBS) associated with influenza vaccination has been observed in a minority of influenza seasons over the last two decades. Apart from the 1976-1977 swine flu season, the risk of GBS associated with influenza vaccination is small. In a retrospective study of the 1992-1993 and 1993-1994 seasons in four American states(55), the relative risk of GBS occurring within 6 weeks after influenza vaccination, adjusted for age and sex, was 1.7 (95% confidence intervals 1.0, 2.8; p = 0.04), suggesting slightly more than one additional case of GBS per million persons vaccinated against influenza. In comparison, the morbidity and mortality associated with influenza are much greater. In Canada the background incidence of GBS was estimated at just over 20 cases per million population in a study done in Ontario and Quebec(56). A variety of infectious agents, such as Campylobacter jejuni, have been associated with GBS. It is not known whether influenza virus infection itself is associated with GBS. It is also not known whether influenza vaccination is causally associated with increased risk of recurrent GBS in persons with a previous history of GBS. Avoiding subsequent influenza vaccination of persons known to have developed GBS within 6 to 8 weeks of a previous influenza vaccination appears prudent at this time. Influenza vaccine is not known to predispose to Reye's syndrome. Please refer to the Canadian Immunization Guide(10) for further details about administration of vaccine and management of adverse events. Contraindications and precautions Influenza vaccine should not be given to people who had an anaphylactic reaction to a previous dose or with known anaphylactic hypersensitivity to eggs manifested as hives, swelling of the mouth and throat, difficulty in breathing, hypotension and shock. Individuals with acute febrile illness usually should not be vaccinated until their symptoms have abated. Although influenza vaccination can inhibit the clearance of warfarin and theophylline, clinical studies have not shown any adverse effects attributable to these drugs in people receiving influenza vaccine. Simultaneous administration of other vaccines Influenza vaccine may be given at the same time as other vaccines, provided different sites and administration sets (needle and syringe) are used. The target groups for influenza and pneumococcal vaccination overlap considerably. Health care providers should take the opportunity to vaccinate eligible persons against pneumococcal disease when influenza vaccine is given. Pneumococcal vaccine, however, is usually given only once, whereas influenza vaccine is given annually. Storage Influenza vaccine should be stored at 2o C to 8o C and should not be frozen. Strategies for Reducing the Impact of InfluenzaThe effectiveness of influenza vaccine varies depending upon the age and immunocompetence of the vaccine recipient, the degree of similarity between the virus strain included, and the strain of circulating virus during the influenza season. With a good match, influenza vaccination has been shown to prevent laboratory-confirmed influenza illness in approximately 70% to 90% of healthy children and adults. Under these circumstances, studies have also shown influenza vaccination to be approximately 70% effective in preventing hospitalization for pneumonia, and influenza among elderly persons living in the community. Studies among elderly persons residing in nursing homes have shown influenza vaccination to be 50% to 60% effective in preventing hospitalization and pneumonia and <= 85% effective in preventing death, even though efficacy in preventing influenza illness may often be in the range of 30% to 40% among the frail elderly. Vaccination is recognized as the single most effective way of preventing or attenuating influenza for those at high risk of serious illness or death. Influenza vaccine programs should aim to vaccinate at least 90% of eligible recipients. Nevertheless, only 70% to 91% of long-term care facility (LTCF) residents and 20% to 40% of adults and children with medical conditions listed previously receive vaccine annually(9,57-60). Studies of HCWs in hospitals and LTCFs have shown vaccination rates of 26% to 61%(58-61). This low rate of utilization is due both to failure of the health care system to offer the vaccine, and to refusal by persons who fear adverse reactions or mistakenly believe that the vaccine is either ineffective or unnecessary. HCWs and their employers have a duty to actively promote, implement and comply with influenza immunization recommendations in order to decrease the risk of infection and complications in the vulnerable populations they care for(62-64). Educational efforts aimed at physicians and the public should address common concerns about vaccine effectiveness and adverse reactions. These include the beliefs of patients at risk, health care workers and other service providers that they rarely get influenza, the fear of side effects from the vaccine, and doubt about the efficacy of the vaccine. The advice of a health care provider is often a very important factor affecting whether a person is immunized or not. Most people at high risk are already under medical care and should be vaccinated during regular fall visits. Strategies to improve coverage include the following:
Vaccination of HCWs In order to protect vulnerable patients in an outbreak situation, it is reasonable to exclude from direct patient care HCWs who develop confirmed or presumed influenza, and unvaccinated HCWs who are not on antiviral prophylaxis. Health care institutions should have policies in place to deal with this issue. Transmission of influenza between clinically or subclinically infected HCWs and their vulnerable patients results in significant morbidity and mortality(5,66). In the absence of contraindications, refusal of HCWs to be immunized implies failure in their duty of care to their patients. Studies have demonstrated that HCWs who are ill with influenza frequently continue to work(30,66). In a British study, 59% of HCWs with serologic evidence of recent influenza infection could not recall having influenza, suggesting that many HCWs experience subclinical infection(67). These individuals continued to work, potentially transmitting infection to their patients. In addition, absenteeism of HCWs who are sick with influenza results in excess economic costs and in some cases, potential endangerment of health care delivery due to scarcity of replacement workers. Vaccination of HCWs in health care facilities has been shown to reduce total patient mortality, influenza-like illness, and serologically confirmed influenza(29-31). Influenza vaccination programs for HCWs may also result in cost savings and reduced work absenteeism, depending on factors including disincentives to take sick days, strain virulence and the match between infecting strain and vaccine(31,34,67-69). Recommendations for the Prophylactic Use of AmantadineAmantadine hydrochloride is an antiviral agent that interferes with the replication cycle of type A (but not type B) influenza viruses. The following are recommendations for its use in prophylaxis. Use of amantadine for therapy of patients with influenza is not discussed in this statement. Currenttly (i.e., at the time of writing of this statement), in Canada, the only drug currently approved for the specific prophylaxis of influenza virus infections is amantadine hydrochloride. It is 70% to 90% effective in preventing illness caused by type A influenza viruses, but is ineffective against type B strains. Because antiviral agents taken prophylactically may prevent illness but not subclinical infection, some persons who take these drugs may still develop immune responses that will protect them when they are exposed to antigenically-related viruses in later years. However, amantadine prophylaxis should not replace annual influenza vaccination in groups for whom vaccine is recommended. During influenza outbreaks, increased prevalence of amantadine resistance has been reported in families and within semi-closed settings including nursing homes. Amantadine resistance is more likely to occur in populations where the drug is used for both prophylaxis and treatment, as opposed to prophylaxis alone(70). Failure to adequately isolate institutional patients on amantadine therapy also increases the probability of transmission of any resistant virus that may emerge, which in turn, may result in prolongation of an epidemic or a second epidemic wave(70). Amantadine prophylaxis may be used as follows:
Factors including local epidemiology, potential side effects, concern regarding emergence of viral resistance, adherence to medication regimens and cost may be considered in decisions regarding the duration of amantadine prophylaxis(70,71). Dosage recommendations for prophylaxis of influenza A infection with amantadine are presented in Table 2; however, the package insert should be read for complete information. Any adjustments for renal function should be made in addition to adjustments for age. Particular caution should be paid to dosages in those > 65 years of age, among whom some degree of renal impairment is common. Dosages may be adjusted according to calculated or laboratory-confirmed creatinine clearance. It should be noted that although Table 2 presents the recommended dosage schedule for amantadine prophylaxis, a few studies suggest that a prophylactic dose of 100 mg daily in individuals 10 to 64 years of age, and in children weighing > 20 kg, who have normal renal function, may be as effective as the recommended dose of 200 mg daily(72). While use of this dosing schedule, when properly adhered to, has been effective in controlling institutional influenza A outbreaks, the intermittent dosages may be confusing. A proposed new once- daily dosage regimen for persons > 65 years of age, based on renal function, was recently published in the Canadian Journal of Infectious Diseases(73), and is reproduced in Table 3. This dosage regimen has not yet been field tested, but pharmokinetic modelling suggests that it should be as effective and safe as the standard regimen presented in Table 2. HCWs and influenza program planners will need to assess the advantages and disadvantages of the two different schedules when selecting a regimen for their patients. Although they have not been licensed for prophylactic use in Canada at the
time of writing of this statement, neuraminidase inhibitors have been used
under study conditions for this purpose in institutional outbreaks(73-77).
During institutional outbreaks of influenza, situations in which neuraminidase
inhibitors may be indicated as prophylactic agents under appropriate study
(off-licence) conditions, include outbreaks of influenza B, as well as illness
among residents who are at risk of serious side effects from amantadine(73).
Precautions In otherwise healthy young adults given amantadine prophylaxis, 5% to 10% report difficulty concentrating, insomnia, light-headedness, and irritability. These side effects are usually mild and cease shortly after the prophylaxis is stopped; however, they can be more frequent in the older population unless a reduced dosage is used. Serious side effects (e.g., marked behavioural changes, delirium, hallucinations, agitation, seizures) have been associated with high plasma drug concentrations. These have been observed most often among persons who have renal insufficiency, seizure disorders, or certain psychiatric disorders, and among elderly persons who have been taking amantadine as prophylaxis at a dose of 200 mg/day. Lowering the dosage among these persons is effective in reducing the severity of such side effects. Amantadine is eliminated from plasma wholly by renal tubular secretion and glomerular filtration; it is not metabolized by the liver. Therefore in people with reduced renal function, particularly the elderly, toxic levels can occur if the dosage is not reduced. Recommended prophylactic dosages, by age and renal function, are shown in Table 2. In patients with dialysis-dependent renal failure, the half-life of amantadine is 200 (± 36) hours(78). It should be noted that the calculated creatinine clearance is reasonably accurate for those with a creatinine clearance > 40 mL/min, and those with a stable serum creatinine and muscle mass. However, the calculation becomes less accurate when these conditions are not met. In particular, elderly persons with renal impairment and low muscle mass may have a serum creatinine in the normal range and an estimated creatinine clearance that is higher than the true value. Physicians who prescribe amantadine must be familiar with the limitations of formulas to estimate creatinine clearance, and make clinical decisions regarding dosage adjustments based on these considerations. Amantadine dosage should be reduced in people with a seizure disorder in order to avoid the risk of increased frequency of seizures, and these individuals should be closely observed. Drug interactions have been noted during concurrent administration of amantadine with triamterene and hydrochlorothiazide, trimethoprim-sulphamethoxazole, quinine and quinidine. The patient's age, weight, renal function, co-morbid conditions, current medications as well as the indications for amantadine use should all be considered prior to initiating this medication. Individuals who are given amantadine should be carefully monitored for side effects. AcknowledgementsNACI gratefully acknowledges the following individuals who assisted in the preparation of this statement: Eleni Galanis, Jeannette Macey, Arlene King, Theresa Tam, Yogesh Choudhri, David Scheifele, Danuta Skowronski, Robert Pless, Laszlo Palkonyay, Claude Dubuc and Nicole Boulianne. References
* Members: Dr. V. Marchessault (Chairperson), Dr. J. Spika (Executive Secretary), J. Brousseau (Administrative Secretary), Dr. I. Bowmer, Dr. G. De Serres, Dr. S. Dobson, Dr. J. Embree, Dr. I. Gemmill, Dr. J. Langley, Dr. M. Naus, Dr. P. Orr, Dr. B. Ward, A. Zierler. Liaison Representatives: S. Callery (CHICA), Dr. J. Carsley (CPHA), Dr. V. Lentini (DND),Dr. M. Douville-Fradet (ACE), Dr. T. Freeman (CFPC), Dr. R. Massé (CCMOH), Dr. J. Salzman (CATMAT), Dr. L. Samson, (CIDS), Dr. D. Scheifele (CAIRE), Dr. M. Wharton (CDC). Ex-Officio Representatives: Dr. A. King (CIDPC), Dr. L. Palkonyay (BBR), Dr. P. Riben (MSB). This statement was prepared by Dr. P. Orr and approved by NACI. [Canada Communicable Disease Report]
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Last Updated: 2001-08-13 |