Monday, September 30, 2013

Influenza vaccine

From Wikipedia, the free encyclopedia

Model of Influenza Virus from U.S. National Institutes of Health
The influenza vaccination is an annual vaccination using a vaccine specific for a given year to protect against the highly variable influenza virus.[1] Each seasonal influenza vaccine contains antigens representing three or four influenza virus strains: one influenza type A subtype H1N1 virus strain, one influenza type A subtype H3N2 virus strain, and either one or two influenza type B virus strains.[2] Influenza vaccines may be administered as an injection, also known as a flu shot, or as a nasal spray.
The U.S. Centers for Disease Control and Prevention recommend that everyone over the ages of 6 months should receive the seasonal influenza vaccine.[3] Vaccination campaigns usually focus on people who are at high risk of serious complications if they catch the flu, such as the elderly and people living with chronic illness or those with weakened immune systems, as well as health care workers.[3][4]
Most flu vaccines provide significant protection against the virus.[5] Despite somewhat limited research, the safety of flu vaccines is reassuring; there is no evidence that they can cause serious harm, and no reason for serious side effects to be a concern.[5]

Purpose and benefits of annual flu vaccination

In one study of the elderly, flu vaccines cut the risk of death from influenza in half, and reduced the chance of hospitalization by more than a quarter.[6][7]
According to the CDC, getting the flu vaccine is the best way to protect yourself against the flu and to help prevent its spread throughout the community. The flu vaccine can also reduce the severity of the flu even if a person contracts a strain of the flu that the vaccine did not contain.[8]

Deadly epidemics each winter

An influenza epidemic emerges during flu season each winter. There are two flu seasons annually, corresponding to the occurrence of winter in the Northern and Southern Hemispheres (winter in one hemisphere is at the same time as summer in the other).
Although difficult to assess, these annual epidemics are thought to result in between three and five million cases of severe illness and between 250,000 and 500,000 deaths every year around the world.[9] Tens of thousands of Americans die in a typical flu season, but there are notable variations from year to year. In 2010 the Centers for Disease Control and Prevention (CDC) in the United States changed the way it reports the 30-year estimates for deaths from influenza. They are reported as a range from a low of about 3,300 deaths to a high of 49,000 per year over the past 30 years.[10][11]
The majority of influenza-caused deaths in the industrialized world occur in adults aged 65 and over.[4] A review at the National Institute of Allergy and Infectious Diseases (NIAID) division of the National Institutes of Health (NIH) in 2008 concluded that "Seasonal influenza causes more than 200,000 hospitalizations and 41,000 deaths in the U.S. each year, and is the seventh leading cause of death in the U.S."[12] The average total economic costs caused by the annual influenza outbreak in the U.S. have been estimated at over $80 billion.[13][14]
The number of annual influenza-related hospitalizations is many times the number of deaths.[15] "The high costs of hospitalizing young children for influenza creates a significant economic burden in the United States, underscoring the importance of preventive flu shots for children and the people with whom they have regular contact..."[16] The CDC has projected that a total of 38 million days of school were missed by American students due to the flu.[17]
In 2006, the United States began recommending influenza vaccinations for preschoolers, but Canada did not follow suit until 2010, "thereby creating a natural experiment to evaluate the effect of the policy in the United States."[18] Studying the interim from the 2006 recommendation by the US and until 2010 when the Canadian recommendation to vaccinate preschoolers was initiated, a Canadian study found emergency room (ER) visits significantly lower for 2- to 4-year-olds in Boston than in Montreal (34% fewer ER trips). Vaccination of preschoolers may have reduced their likelihood of transmission of flu to older siblings and raised the chances that their parents would vaccinate older children as well, since there were also 18 percent fewer emergency room visits by 5- to 18-year-olds in Boston than Montreal during the study period.[19]
In another six-year observational study, vaccination of children aged six months through five years was found to prevent illness in more than half.[20]

National advice on flu vaccination

In 2008, the National Advisory Committee on Immunization, the group that advises the Public Health Agency of Canada, recommended that everyone aged 2 to 64 years be encouraged to receive annual influenza vaccination, and that children between the age of six and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.[21]
In the United States, "Routine influenza vaccination is recommended for all persons aged ≥ 6 months."[22][23]
Within its blanket recommendation for general vaccination in the United States, the Centers for Disease Control and Prevention (CDC), who began recommending the influenza vaccine to health care workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers:
Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications.[24]
Influenza vaccine has been demonstrated to prevent disease and death, both in numerous controlled studies and in painstaking scientific reviews of these studies. The CDC reports that studies demonstrate that vaccination is a cost-effective counter-measure to seasonal outbreaks of influenza.[25] The CDC in 2010, after a review of extant studies, extended its guidelines to recommend that every child over 6 months be given the influenza vaccine.[26]

Benefits of vaccination

According to research published in July 2010, vaccination against influenza is also thought to be important for members of high-risk groups who would be likely to suffer complications from influenza, for example pregnant women[22][27] and children and teenagers from six months to 18 years of age;[28]
In raising the upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications[29]
An added expected benefit would be indirect: reducing the number of influenza cases among parents and other household members, and possibly spread to the general community.[29]
Vaccination of school-age children has a strong protective effect on the adults and elderly with whom the children are in contact.[30] Children born to mothers who received flu vaccination while pregnant are strongly protected from having to be hospitalized with the flu. "The effectiveness of influenza vaccine given to mothers during pregnancy in preventing hospitalization among their infants, adjusted for potential confounders, was 91.5%."[31]
For healthy, working adults, influenza vaccines can provide moderate protection[citation needed] against virologically confirmed influenza, but such protection is greatly reduced or absent in some seasons. Evidence for protection in adults aged 65 years or older is lacking. New vaccines with improved clinical efficacy and effectiveness are needed to further reduce influenza-related morbidity and mortality.[32]
Influenza vaccination has been shown highly effective in health care workers (HCW), with minimal adverse effects. In a study of forty matched nursing homes, staff influenza vaccination rates were 69.9% in the vaccination arm versus 31.8% in the control arm. The vaccinated staff experienced a 42% reduction in sick leave from work (P=.03).[33] A review of eighteen studies likewise found a strong net benefit to health care workers.[34] Of these eighteen HCW studies, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of health care worker vaccination correlated with reduced patient deaths.[34] An analysis of data and patient population health in New Mexico's 75 long-term care facilities nursing homes found that as vaccination rates of health care personnel with direct patient contact rose from 51 to 75 percent, the chances of a flu outbreak among patients in that facility went down by 87 percent. The New Mexico study showed that vaccinating health care personnel provided more protection to residents than vaccinating the residents themselves.[35]
In a 2010 survey of United States healthcare workers, 63.5% reported that they received the flu vaccine during the 2010–11 season, an increase from 61.9% reported the previous season. Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and nurse practitioners (82.6%).[36][37][38]
It is important to note that the flu vaccine takes about two weeks to build up enough antibodies to protect against the flu (thus making the vaccinated person protected against the disease),[2] and that the vaccine does not protect against every strain of the flu.[2]


Flu vaccination may lead to side effects such as runny nose and sore throat, which can last for up to several days. Egg allergy may also be a concern, since flu vaccines are typically made using eggs,[39][40] however research into egg-allergy and influenza vaccination [41] has lead some advisory groups to recommend vaccine delivery protocols for egg allergic persons.[42] Some injection-based flu vaccines intended for adults in the United States contain thiomersal (also known as thimerosal), a mercury-based preservative. Despite some controversy in the media,[43] the World Health Organization's Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration.[44]
Although Guillain-Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain-Barré.[45][46] Getting infected by influenza itself increases both the risk of death (up to 1 in 10,000) and increases the risk of developing Guillain-Barré syndrome to a much higher level than the highest level of suspected vaccine involvement (approx. 10 times higher by 2009 estimates).[47][48]
A review has concluded that the 2009 H1N1 ("swine flu") vaccine has a safety profile similar to that of seasonal vaccine.[49] Although one review gives an incidence of about one case per million vaccinations,[50] a large study in China, reported in The New England Journal of Medicine covering close to 100 million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain-Barre syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects; "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination."[51][52]

Efficacy and effectiveness

A vaccine is assessed by its efficacy, the extent to which it reduces risk of disease under controlled conditions, and its effectiveness, the observed reduction in risk after the vaccine is put into use.[53] In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness, which is not always caused by influenza.[54] Influenza vaccines generally show high efficacy, as measured by the antibody production induced in animal models or vaccinated people,[55] or most rigorously, by immunizing healthy adult volunteers and then challenging them with virulent influenza virus.[56] However, studies on the effectiveness of flu vaccines in the real world are uniquely difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses.[57] However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains,[58] and even a mis-matched vaccine can often provide cross-protection.[59]
Nevertheless, multiple clinical trials of both live and inactivated influenza vaccines against seasonal influenza have been performed and their results pooled and analyzed in several 2012 meta-analyses. Studies on live vaccines have very limited data, but these preparations may be more effective than inactivated vaccines.[56] The meta-analyses examined the efficacy and effectiveness of inactivated vaccines against seasonal influenza in adults,[54] children,[60] and the elderly.[61][62] In adults, vaccines show a three-quarters reduction in risk of contracting influenza (4% influenza rate among the unvaccinated versus 1% among vaccinated persons) when the vaccine is perfectly matched to the virus and a one-half reduction (2% get flu without vaccine versus 1% with vaccine) when it is not, but no significant effect on the rate of hospitalization.[54] However, the risk of serious complications from influenza is small in adults, so unless the effect from vaccination is large it might not have been detected. In children, vaccines again showed high efficacy, but low effectiveness in preventing "flu-like illness". In children under the age of two the data are extremely limited, but vaccination appeared to confer no measurable benefit.[60] In the elderly, while many individual studies show effectiveness,[63][64][65] the overall evidence is still insufficient evidence to draw clear conclusions on the effectiveness of vaccination,[61][62][66][67] including a new high-dose flu vaccine specificially formulated to provide a larger immune response.[68] Available evidence indicates that the high-dose vaccine produces a stronger immune response, and a study designed to determine the effectiveness of Fluzone High-Dose in preventing illness from influenza compared with Fluzone is expected to be completed in 2014–2015.[69]
During an influenza pandemic, where a single strain of virus is responsible for illnesses, an effective vaccine could produce a large decrease in the number of cases and be highly effective in controlling an epidemic.[70] However, such a vaccine would have to be produced and distributed rapidly to have maximum effect.[71] Such distribution challenges may be met, with good success.[citation needed] Overall, vaccines against the 2009 H1N1 influenza pandemic were found to be effective in a Scottish study.[72]
A 2011 meta-study published in the journal The Lancet, "Efficacy and Effectiveness of Influenza Vaccines," analyzed 31 prior studies on the effectiveness of influenza vaccination trials conducted between 1967 and 2011. The analysis found that flu shots were efficacious 67 percent of the time; the populations that benefited the most were HIV-positive adults ages 18 to 55 (76 percent), healthy adults ages 18 to 46 (approximately 70 percent) and healthy children ages 6 to 24 months (66 percent).[67]
The group most vulnerable to non-pandemic flu, the elderly, is also the least to benefit from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age.[73] In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over age 65 is over ten times more likely to die an influenza-associated death than the 50–64 age group.[74]
As mortality is also high among infants who contract influenza, the household contacts and caregivers of infants should be vaccinated to reduce the risk of passing an influenza infection to the infant.[4] Data from the years when Japan required annual flu vaccinations for school-aged children indicate that vaccinating children—the group most likely to catch and spread the disease—has a strikingly positive effect on reducing mortality among older people, due to herd immunity: one life saved for every 420 children who received the flu vaccine.[75] However, a 2010 Cochrane review found that the same benefit did not extend to vaccinating health care workers working with elderly patients in long-term care facilities.[76] In working adults, by contrast, Cochrane found that vaccination reduced both influenza symptoms and working days lost, without affecting transmission or influenza-related complications.[54]

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