Influenza and Pneumococcal Vaccinations in the Emergency Department

Tetanus immunizations in the emergency department 

Although it is generally recommended that immunizations be administered by patients' private physicians, immunizations against organisms, such as tetanus, hepatitis, and rabies, have been administered in the ED for years. One analysis using the National Hospital Ambulatory Medical Care Survey from 1992 to 2000 showed that EDs gave 27,738,000 vaccines and 93% were against tetanus [3]. One recent study performed at five university-affiliated EDs (1999–2000) reported a seroconversion rate of 90.2% [4]. Although it is not clear precisely when tetanus immunization in the ED began, it is clear that this is common practice and standard of care for patients who have wounds. In fact, tetanus immunizations have been administered in the ED since the 1970s and the beginning of organized emergency medicine as a specialty. The CDC reported an annual incidence of 0.16 cases per million population, or an average of 43 cases per year [5]. Although uncommon in developed countries, such as the United States, tetanus remains a much larger problem in developing countries, with some estimates of 1 million cases worldwide each year [6]. The World Health Organization (WHO) estimated that there were 309,000 deaths from tetanus in 2000, and 200,000 of these were estimated to have occurred from neonatal tetanus [7]. These reports clearly show a reduced incidence in developed countries and a much lower case fatality rate in patients who have up-to-date tetanus toxoid immunization status. From these large numbers of tetanus immunizations given in EDs and in primary care physicians' offices, one can conclude that our current emphasis on preventing tetanus has been successful to a large extent. Despite the gravity and impact of influenza and pneumococcal diseases in EDs and the relatively rare cases of tetanus, however, the former vaccines remain underused in EDs.

Influenza and pneumococcal immunizations in the emergency department 

Immunizations against influenza and pneumococcal disease have been widely believed to be underused in Americans 65 years of age and older [8], and this has occurred despite the fact that influenza is believed to cause more than 100,000 excess hospitalizations and 20,000 deaths per year [9]. Because hospitalized patients are at particularly high risk for these diseases and many have been hospitalized in the previous 3 to 5 years, the Advisory Committee on Immunization Practices (ACIP) has recommended immunizing eligible hospitalized adults against influenza and pneumococcal diseases as a strategy to increase the rate of vaccination [9], [10]. The process of immunizing hospitalized patients against influenza and pneumococcal diseases has been recommended by the Centers for Medicare and Medicaid Service (CMS) as a method to improve the quality of care given to Medicare beneficiaries [11]. In fact, these vaccinations have been recommended since the 1980s [12], [13]. This practice continues to be recommended today and was part of the combined recommendations by the American Thoracic Society (ATS) and Infectious Diseases Society of American (IDSA) in their most recent guidelines for the treatment of community-acquired pneumonia [2]. Clearly, the administration of influenza and pneumococcal vaccinations to eligible patients has been demonstrated to reduce morbidity and mortality and to save costs [14], [15], [16], [17], [18], [19]. Also, administration of these immunizations to hospitalized patients has become a crucial method to improve these vaccination rates.

From these studies, it follows that vaccination programs based in EDs represent important additional methods of vaccinating eligible patients. Furthermore, of the 119 million patients seen in US EDs, only a relatively small proportion are admitted, and those treated and sent home represent an excellent opportunity to administer influenza and pneumococcal vaccinations, especially because many have no primary care physician. Initially, reports from patients in the ED showed that only approximately 20% of eligible patients in the ED had even heard of pneumococcal immunization and only 8.6% had been immunized [20], [21]. Patients who could identify a primary care provider or a clinic at which they were followed were much more likely to have received pneumococcal and influenza vaccinations. Of the eligible patients in the ED, approximately 60% said they would receive the vaccine in the ED. Subsequent reports continued to verify low immunization rates among eligible patients in the ED, with 75% to 82% of eligible patients in the ED reporting that they had not received pneumococcal vaccinations and 57% to 63% reporting that they had not received influenza vaccinations [22], [23]. More than 50% of patients who had not received previous vaccinations consented to receive the vaccinations in the ED. Similar results were obtained in studies based at four EDs in Canada, and most emergency physicians surveyed were willing to prescribe vaccinations for influenza [24]. A similar study in an inner city county hospital population found that only 3% of high-risk patients had received previous pneumococcal vaccinations [25]. From these studies, it is evident that patients in the ED represent a patient population that is largely underimmunized against pneumococcal disease and influenza; furthermore, more than half of these patients are willing to receive these immunizations in the ED.

From a disease prevention standpoint, many of those patients eventually diagnosed with pneumococcal bacteremia had been previously seen in an ED, often more than once [26]. In one study of patients who had pneumococcal bacteremia, of those with risk factors, nearly 90% had been seen in an ED during the previous 5 years, whereas only approximately half (49.7%) had been on an inpatient medicine ward and only approximately a third (30.6%) had been seen in a general medicine clinic setting [27]. Not only did both studies report that administration of these vaccines in the ED would be cost-effective, but the latter also suggested that a vaccination program in the ED has greater potential to reach more high-risk patients than the general medicine inpatient wards or the general medicine clinic setting.

Arguments for using EDs for administration of influenza and pneumococcal vaccinations have been numerous. According to the National Ambulatory Medical Care Survey, ED visits in our country have increased from 90.3 to 113.9 million visits in 2003 to just more than 119 million visits in 2006 (CDC, personal communications, 2006). The population represented by those older than 65 years of age has increased by 26%, and, similarly, representation of many socioeconomically disadvantaged populations has also increased in the ED. The missed opportunities for immunization of high-risk patients loom larger than ever.

Influenza and pneumococcal disease have more direct effects on EDs, creating more urgent needs for administering influenza and pneumococcal vaccines. Influenza outbreaks were associated with a significant increase in elder (65 years of age and older) persons' use of the ED for influenza-related infections and upper respiratory infections [28]. In this study, the investigators reported that for every 10 new cases of influenza in the community, there was a 1.5% increase in the proportion of elderly patients in the ED who presented with influenza-related infections and upper respiratory infections. During periods in which the CDC declared “widespread influenza activity,” there was generally noted to be a marked increased in resource use [29]. The resources considered included increased admission rate, increased ED length of stay for admitted and discharged patients, increased ED saturation time, and increased numbers of patients who left the ED without being seen. Influenza outbreaks were also associated with increased ambulance diversion [30]. For every 100 cases of influenza per week, ambulance diversion increased by 2.5 hour per week. Other reports demonstrated a substantial increase in ED visits during influenza outbreaks, especially for patients who had respiratory illnesses, such as influenza, pneumonia, and exacerbations of chronic lung diseases [31]. These data suggest that, clearly, pneumococcal and influenza infections contribute to all the complications associated with ED overcrowding.

Several organizations also recommend strategies for administration of immunizations in EDs. The CDC and ACIP have recommended initiating influenza and pneumococcal immunizations in the ED for years. In 1998, at the American College of Emergency Physicians (ACEP) annual council meeting, a resolution was passed asking the ACEP to address this issue and endorse the immunization of high-risk populations in our EDs [32]. Subsequent ACEP policy statements to address this issue were made in 2000 and 2002. The 2000 policy statement recommended that health care workers be immunized and that high-risk patients be identified and appropriately referred [33]. It was recommended that EDs should consider administering vaccinations in the elderly if no other resources are available, especially if there is a widespread outbreak or epidemic. The 2002 ACEP Policy statement simply stated that the ACEP supports the immunization of high-risk patients in the ED against pneumococcal disease and influenza [34].

Not only has administration of pneumococcal and influenza vaccinations been demonstrated to be cost-effective, but Medicare Part B pays or reimburses for administration of these vaccines at a rate beyond the inpatient diagnosis-related group payment for hospitalized patients [35]. The reimbursement for these vaccines has been made even easier, because billing can be accomplished through roster billing, wherein hospitals or health care providers need only submit a list of patient names and Medicare numbers [36].

Pediatric influenza and pneumococcal immunizations in the emergency department 

Unlike adults, children are not generally underimmunized in the United States. Childhood immunization rates are currently at record levels and approaching CDC and ACIP Healthy People 2010 goals [37]. Pneumococcal and, to a much greater extent, influenza immunization rates continue to lag behind more traditional childhood immunizations, however. Surprisingly, influenza vaccination is not currently part of the baseline series of vaccinations so effectively administered by US health care providers [38]. Although rates of pneumococcal immunizations have increased since 2005, and the literature has demonstrated a decrease in pneumococcal disease [39], [40], influenza immunization rates remain low.

In 2006, the ACIP expanded its recommendations for routine influenza vaccination of healthy children from the age of 6 months to 5 years [41]. In 2007, using data from several sentinel sites, the CDC found that approximately 30% of children aged 6 to 23 months and approximately 20% of children aged 2 to 5 years were appropriately vaccinated. The study also reported high geographic and socioeconomic variability not associated with other childhood immunization programs [42]. In children younger than 2 years of age, those with comorbidities, and those in undeveloped countries, influenza and pneumococcal infections can cause significant childhood mortality and morbidity secondary to severe pneumonia, meningitis, and bacteremia [43]. Influenza and pneumococcal infections are often concomitant and are, to a large extent, vaccine preventable [44].

There is also a significant socioeconomic burden on the community associated with pediatric influenza because of missed school, work absenteeism, more doctors' appointments, increased antibiotic use, and other influenza-related costs in children with verified influenza versus other respiratory infections [45]. Influenza-infected children also shed virus for longer periods than do adults, and are therefore considered to be more infectious to the general population [46]. Pediatric populations visiting EDs are underimmunized compared with the general pediatric population [47], and more than 75% of frequent pediatric ED users have chronic underlying disease [48]. Despite the evidence for ED-based influenza and pneumococcal immunization programs for pediatric patients and the demonstrated effectiveness of these programs, controversy exists because of the desire by some pediatric and family physicians to keep pediatric immunizations part of primary care [49], [50], [51], [52].

Other potential benefits of influenza and pneumococcal immunizations in the emergency department 

The influenza vaccine has been reported to decrease mortality and morbidity in persons with cardiovascular disease (CVD) and to prevent asthma exacerbations in children. The evidence is compelling in regard to CVD, but the balance of evidence suggests that influenza vaccination may instead be linked to increased rates of asthma exacerbation in children.

In persons older than 65 years of age with CVD, influenza vaccination has been reported to result in a 60% reduction in death from all causes. This includes death from myocardial infarction (MI), cerebrovascular accident (CVA), and congestive heart failure (CHF) exacerbations. Strong evidence for CVD protection comes from the Flu Vaccination in Acute Coronary Syndromes (FLUVACS) trial. This prospective randomized study showed a relative risk reduction of a composite end point (cardiovascular death, nonfatal MI, or severe ischemia) to be 0.59% (95% confidence interval [CI]: 0.30 to 0.86; 11% [nonimmunized] versus 23% [immunized]) [53]. There are other well-designed studies that refute any reduction in the risk for MI specifically [54]. Severe pneumonia has consistently been associated with increased rates of CVA and exacerbation of CHF symptoms and is thought to accelerate atherosclerotic processes. Strong convincing evidence for a direct cause-and-effect relation between severe respiratory infection and CVA has not been statistically established, however. In 2006, the American Heart Association (AHA) and the American College of Cardiology (ACC) recommended influenza vaccination as a secondary prevention measure in adults and children with known CVD. There is no evidence to suggest that influenza vaccination is harmful to persons with CVD.

Influenza vaccination has been evaluated in children for reduction of acute asthma exacerbation. There have been four major studies: three were retrospective cohort studies, and one was a prospective placebo-controlled trial [55]. Two of three cohort studies showed an increase in the number of acute exacerbations. One cohort study by Smits and colleagues [56] did show protective effect in children younger than 6 years of age. The prospective trial did not show benefit and did show a nonsignificant trend toward harm in children with asthma. Although the results of the cohort studies were negative, the studies were subject to considerable bias and may not reflect real-world clinical conditions. Despite a lack of clear evidence, the US Department of Health and Human Services (DHHS) advocates routine influenza immunization for children younger than 6 years of age with all clinical subtypes of asthma [57], [58].

Influenza 

The influenza virus is one of the most common infectious diseases worldwide. It is estimated that between 20 and 50 million people died worldwide from the H1N1 type influenza pandemic that occurred in 1918 to 1919. There were approximately 670,000 deaths in the United States [58]. Influenza has untold effects on the economy, health care system, and human suffering.

Epidemics generally occur in the winter months and often affect millions of people each year in the United States. Influenza occurs year round in the tropics. The frequency and severity depend on the virulence of the virus subtype [59]. The CDC estimates that 20,000 deaths occur annually in the United States as a result of influenza infection. Adults older than 50 years of age, those with chronic medical conditions, and children younger than 2 years of age are at higher risk for severe complications, namely, pneumonia [42].

Influenza is an acute febrile illness that can be challenging to diagnose secondary to a highly variable presentation. Many patients present early, before significant prostration, with signs and symptoms consistent with a common upper respiratory infection. Alternatively, many patients at highest risk for severe disease also have comorbidities that can obfuscate the clinical picture. One symptom that does seem to predict influenza independently is disproportionate prostration [60]. Death is usually associated with severe secondary bacterial pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, or Staphylococcus aureus.

The virus is highly contagious and is spread by large droplets and small-particle aerosols from the respiratory tract of infected individuals. Adult patients are generally infected 1 to 2 days before symptom presentation and are contagious because of viral shedding for approximately 1 day before and 5 to 10 days after presentation [61]. School- aged children (especially 5–9 years old) typically shed for longer periods and represent a major source of infection in the community, especially to the elderly, who are at greatest risk for severe infection [46].

Influenza is a zoonotic infection caused by a single-stranded RNA virus with three major subtypes (A, B, and C), which are classified within the family Orthomyxoviridae. Major virulence factors are the surface proteins hemagglutinin and neuraminidase, and are thus targets for pharmacotherapeutic treatments. Influenza type A is the most pathogenic and causes the greatest human disease burden. The most common influenza A subtypes are H1N1 and H3N2. The trivalent inactive vaccine (TIV), which is developed annually and is used worldwide, contains A strains from H1N1, H3N2, and one influenza B strain.

Pandemics occur when the influenza virus acquires a new genetic code for hemagglutinin or neuraminidase proteins. The encoding of hemagglutinin and neuraminidase by separate RNA molecules facilitates the reassortment of these genes in animals simultaneously infected by two different subtypes. Theoretically, reassortment can occur in human beings with dual infections. The abrupt genetic change is called antigenic shift. Until these new proteins are identified and incorporated into vaccines, there can be no large-scale immunity. New virus configurations may confer severe virulence with increased infectivity and profound mortality and morbidity [62].

Epidemics occur when there are missense mutations in the hemagglutinin and, to a lesser extent, the neuraminidase genes, altering the epitope so that the virus is not recognized by circulating acquired antibodies. The gradual accumulation of new epitopes on the hemagglutinin and neuraminidase proteins is called antigenic drift. In the immunocompetent host, influenza infection elicits a strong immune response against only the specific strain that caused it. Within a brief period, antigenic drift makes one susceptible to a new viral variant. Mass immunization with influenza vaccines has proven to be helpful in reducing the size and severity of new epidemics [63].

The WHO Global Influenza Surveillance Network was established in 1952. The network consists of several hundred organizations that collectively perform regional primary virus isolation and preliminary antigenic characterization. New strains are isolated and evaluated for high-level antigenic and genetic analysis. The pooled data, along with expert consensus, form the basis for WHO recommendations on the formulation of influenza vaccines. Different vaccine formulations are developed for the Northern and Southern Hemispheres [64].

Influenza vaccines 

The influenza vaccine should ideally be administered in September through November and especially in high-risk groups. This schedule provides adequate time for immunogenic response before the influenza virus arrives in the community (United States). Because peak influenza season in the United States is January through March, immunizations should continue as long as vaccine is available [42].

There are two basic types of influenza vaccines: inactive and live-attenuated virus vaccines. The first to be developed and the most commonly used vaccine currently consists of one of three subtypes of inactive virus (killed viruses): (1) whole-virus vaccines, (2) inactivated virus particles (split-virus vaccines), or (3) purified hemagglutinin protein vaccines. All inactive vaccine formulations contain A strains from H1N1, H3N2, and one influenza B strain, and are thus called TIVs. All inactive virus vaccines are formulated for intramuscular delivery [65].

The second type and, arguably, the most effective vaccine consists of live-attenuated virus and an intranasal delivery system. Both types of vaccines incorporate antigens from the three major viral strains predicted to be in circulation. The live-attenuated virus vaccines are developed to replicate well in the cool physiologic environment found in the upper respiratory system and poorly in the warmer lower respiratory system [42]. The intranasal live-attenuated vaccine formulation is often referred to as a cold-adapted influenza vaccine (CAIV-T).

The influenza vaccine is produced by a small number of manufacturers [42]. The viral antigens are grown in fertilized chicken eggs. In North America, the vaccine is produced by only six manufacturers and is dispensed predominantly in individual-dose vials or intranasal devices. Some newer single-dose vials obviate the need for the use of a mercury-containing compound (thimerosal) traditionally used for preservation and antibiosis in multidose vials. It has been shown by the CDC, with the support of several studies, that there is no correlation between thimerosal and neurologic sequelae, including autism. Despite the CDC position, the US Food and Drug Administration has recently called for the elimination of thimerosal from all formulations [66]. Egg-based vaccines are contraindicated in people with severe allergies to egg protein and those with a history of Guillain-Barré syndrome [67].

Egg-based vaccine production has many limitations when it comes to ramping up for a surge in response to an influenza pandemic. Egg-based production requires having millions of 11-day-old chicken eggs available continuously. This is a dubious process, considering that a major current public health concern (especially in Asia) is avian influenza, which exhibits high lethality in chickens. Despite the current limitations of egg-based production, expert consensus advocates leveraging the egg-based manufacturing infrastructure for pandemic vaccine production while simultaneously and aggressively exploring strategies to improve vaccine immunogenicity, evaluating vaccine adjuvants, and developing larger capacity cell culture–based live-attenuated virus vaccine production and methods to induce durable immunity [68].

Most commercially available viral vaccines (except for influenza) are manufactured using cell culture technology. Cell culture–based production uses bioreactors, which grow viruses in a closed environment utilizing a readily available growth medium. Cell culture–based production is insensitive to having millions of precisely aged chicken eggs, and production could potentially be expanded faster to meet surge capacity. Many governmental organizations, including the DHHS, are promoting and investing worldwide in cell culture–based influenza vaccination production [69].

Both types of vaccines have been well studied. There is, however, considerably more data using the inactivated virus vaccines. Studies have been performed in animal models and prospective human clinical trials, and several meta-analyses have been reported [15], [70]. Testing the efficiency of the vaccine is straightforward. Healthy adults are given the vaccine and then infected with live virus. Antibody production is also measured as an indicator of efficiency.

Both types of vaccines are efficient at producing an immunogenic response. The intranasal live-attenuated virus produces circulating antibodies and a large number of immunoglobulin A (IgA) antibodies in the respiratory mucosa. Mucosal immunity is theoretically more helpful for preventing influenza infection through the respiratory tract [71]. Ethical considerations obviate the ability to test vaccine efficiency in the patient populations at greatest risk for severe disease as a result of the concerns for inducing influenza infections in these patients.

Reporting effectiveness of influenza vaccination with certainty is impossible. There are no prospective clinical trials in the populations at greatest risk. There is a predominance of meta-analyses in the literature, and some questionable statistical methods have driven public health policy [72], [73], [74]. The level of evidence supporting influenza vaccine effectiveness falls short of standards that have been adopted in many other clinical specialties. This being said, public health concerns with endemic influenza, ethical considerations regarding trial design, a rapidly aging population, and the potential magnitude of a severe influenza pandemic do not allow for passive public health policy. Influenza vaccination effectiveness in the literature is controversial and is cited in the context of the best supporting evidence.

In clinical practice, effectiveness is measured in a vaccinated individual as the practical reduction in risk for mortality and morbidity. Data on the effectiveness of influenza vaccination can be delineated into four age groups: (1) immunocompetent adults, (2) the elderly (>65 years of age), (3) children (5–18 years of age), and (4) children younger than 2 years of age.

In the immunocompetent adult, influenza vaccines are highly effective against the viral strains found in the vaccine. There is only a marginal effect on the rate of infection and no effect on the rate of hospitalization, however. This is partially attributable to the large number of mild disease-causing influenza strains and other respiratory viruses found in the community.

Similarly, in children, efficiency is high, but effectiveness is only high in children older than 6 years of age. There is poor effectiveness in children younger than 2 years of age, as demonstrated by a clear increase in mortality and morbidity in this age group [75]. One important phase 3 study in children aged 6 to 59 months showed a risk reduction of 55% in laboratory-confirmed influenza cases [76]. Another systematic review showed that in children younger than 16 years of age, there was a risk reduction of 79% to 80% in laboratory-confirmed influenza and a reduction in clinical illness of 34% to 38% [77].

In the elderly, the efficiency is high and the effectiveness is complex and, in part, socially dependent; vaccination does not alter the rate of infection, but it does decrease the frequency of pneumonia, severe infection, and rate of hospitalization and death from pneumonia. The risk reduction is reported to be 70% to 90%. Reduction in hospitalization is 25% to 39%, and there is a 39% to 75% reduction in death [78]. The effectiveness also seems to be higher in institutionalized elderly persons versus those from the community at large. Among nursing home residents, influenza vaccination can reduce hospitalizations (all causes) by approximately 50%, the risk for pneumonia by approximately 60%, and the risk for death (all causes) by 68% [79] (Box 1, Table 1).

Table 1. Approved influenza vaccines for different age groups—United States

	Vaccine	Generic name	Manufacturer	Preparation	Age group	No. doses	Route
	TIV	Influenza vaccine	Sanofi Pasteur	0.25-mL prefilled syringe	6–35 months	1 or 2a	Intramuscular
				0.5-mL prefilled syringe	36 months and older	1 or 2a	Intramuscular
				0.5-mL vial	36 months and older	1 or 2a	Intramuscular
				5.0-mL multidose vial	6 months and older	1 or 2a	Intramuscular
	TIV	Influenza vaccine	Novartis vaccine	5.0-mL multidose vial	4 years and older	1 or 2a	Intramuscular
	TIV	Influenza vaccine	GlaxoSmith Kline	0.5-mL prefilled syringe	18 years and older	1	Intramuscular
	TIV	Influenza vaccine	GlaxoSmith Kline	5.0-mL multidose vial	18 years and older	1	Intramuscular
	LAIV	Influenza nasal vaccine, live	MedImmune	0.2-mL sprayer	5–49 years	1 or 2b	Intranasal

Abbreviations: LAIV, live attenuated influenza virus vaccine; TIV, trivalent inactivated influenza virus vaccine. Adapted from CDC 2007 to 2008 influenza prevention and control recommendations.

a Two doses administered at least 1 month apart are recommended for children aged 6 months to 8 years who are receiving TIV for the first time, and those who only received one dose in their first year of vaccination should receive two doses in the following year. b Two doses administered at least 6 weeks apart are recommended for children aged 5–8 years who are receiving LAIV for the first time, and those who received only 1 dose in their first year of vaccination should receive 2 doses the following year.

In terms of safety, TIVs and CAIV-Ts are considered safe. The TIV subtypes do exhibit different rates of reactogenicity, however. Whole-virus vaccines exhibit a 15% to 20% rate of local reaction (whole-virus vaccines are not available in the United States). The local reaction is predominantly in young children and is self-limited, rarely lasting longer than 1 to 2 days. Minor systemic reactions, including, fever, malaise, myalgias, cellulites, and serum sickness, occur in less than 3% of vaccine recipients. The reactions are transient and generally occur within 6 to 12 hours of vaccination [42]. As one would expect, split-virus vaccines and subunit vaccines exhibit substantially less systemic reactogenicity. The reduced reactogenicity is found in all age groups [80]. There are certain TIV formulations (namely, the 1979 Northern Hemisphere formulation) that have been associated with a slight but nonsignificant increase in the risk for Guillain-Barré syndrome [81]. The most common side effects from CAIV-Ts are rhinorrhea, fever, myalgias, and mild abdominal pain. The illness pattern is self-limited and is not associated with systemic allergic reactions. Influenza vaccines have been found to be safe in pediatric and adult patients who have HIV [82].

Antiviral therapy and chemoprophylaxis against influenza 

Comprehensive influenza vaccination is clearly the best primary preventative measure against influenza infection. Based on several ED studies mentioned previously [20], [21], [22], [23], [24], [25], [26], [27], we know that many patients in the ED are not being properly immunized. To this end, antiviral drugs can be used clinically to attenuate influenza symptoms and, to a lesser extent, to prevent influenza infection in individuals at high risk who may have not been immunized before the detection of influenza in their community [83].

There are currently two approved antiviral medicines recommended for use in the United States: oseltamivir and zanamivir. They are chemically related antiviral compounds that target neuraminidase and have excellent activity against influenza A and B viruses. Antiviral therapy must be started within 24 to 48 hours after the onset of symptoms. Antiviral therapy can attenuate illness severity and shorten the duration of illness by 24 to 36 hours [84]. Antiviral therapy for influenza may also prevent serious influenza-related complications, but the data supporting this are incomplete [85]. Antiviral medications are reported to be 70% to 90% effective in preventing influenza and are useful adjuncts to vaccination in certain populations [86], [87]. Antiviral medicines are also effective at preventing disease in those using them as chemoprophylaxis with household members with confirmed influenza [88]. Amantadine and rimantadine are no longer recommended by the CDC.

Oseltamivir is approved for the treatment of individuals 1 year of age or older. Zanamivir is approved for the treatment of individuals 7 years of age or older. The recommended duration of treatment with oseltamivir or zanamivir is 5 days. Oseltamivir is licensed for use as chemoprophylaxis in people 1 year of age or older. Zanamivir is licensed for use as chemoprophylaxis in people 5 years of age or older. To be effective as prophylaxis, antiviral therapy must delivered for the duration of exposure to individuals with influenza or until immunity after vaccination develops. It generally takes 2 weeks to develop acquired antibodies in adults, and it can take significantly longer in children depending on age and health status. The supply and cost of antiviral therapy significantly limit their utility in epidemics and pandemic situations and underscore the role of vaccination as the primary preventive measure against influenza.

Pneumococcal disease 

Pneumococcal disease is a leading cause of serious illness, hospitalization, and death in children and adults worldwide. Pneumococcal disease causes upper and lower respiratory tract infections and invasive systemic disease. Pneumococcus is an encapsulated gram-positive bacterial organism. The disease process is primarily a result of massive bacterial replication because it has few significant virulence factors. Encapsulation does allow the bacterial organism to avoid phagocytosis, amplifying its ability to replicate and stimulate a complex inflammatory cascade.

In the United States, pneumococcal disease is responsible for causing most cases of community-acquired bacterial pneumonia (>500,000 cases a year), bacteremia (>50,000 cases a year), and meningitis (>3000 cases a year) [89]. Pneumococcus also causes otitis media (>7 million cases a year) and sinusitis [90]. The incidence of invasive pneumococcal disease is significantly higher in the developing world than in industrialized nations [91]. There are manifold pneumococcal types (>90); the 10 most common types account for approximately 62% of invasive disease worldwide [92].

Pneumococcal disease is more common in winter months and when respiratory viruses, such as influenza, are prevalent. Endemic pneumococcal disease is not common but can occur in institutionalized patient populations and in school children. In the United States, most deaths from pneumococcal disease occur in the elderly, although in developing countries, child mortality is still high. In 2000, a new pneumococcal conjugate vaccine (PCV) was introduced in the United States for routine childhood immunization and has dramatically reduced the incidence of severe pneumococcal disease in children [93]. During the same time, rates of childhood immunization have also dramatically increased. Pediatric pneumococcal immunization in the United States is currently approximately 87% [37]. Because PCV interrupts person-to-person transmission, the incidence of severe pneumococcal disease in older children and adults has also declined [93]. Pneumococcal vaccination is recommended by all major clinical advisory groups including the CDC, AICP, ACEP, and Cochrane Database of Systematic Reviews [94].

Pneumococcal disease is a febrile illness in most forms of pneumococcal infection and may account for the only symptoms in pediatric patients who have bacteremia. Patients who have pneumococcal pneumonia typically have cough, dyspnea, or pleuritic chest pain and may have shaking chills. Fever and sputum production may be absent in elderly persons with pneumococcal pneumonia. Pneumococcal meningitis, otitis media, or sinus infections may present with signs consistent with other bacterial or viral infections.

Two vaccines are currently available in the United States to prevent pneumococcal disease: (1) the pneumococcal conjugate vaccine 7 (PCV7) and (2) the pneumococcal polysaccharide vaccine 23 (PPV23). Both vaccines are effective at inducing antibodies to pneumococcal capsular proteins and are effective at preventing invasive disease [95]. The PCV7 prevents some pneumonia and otitis media and sinusitis in children [96].

The PCV7 is part of the routine infant immunization schedule in the United States and is recommended for all children younger than 2 years of age and for children 2 to 4 years of age who have certain underlying conditions [10]. Pediatric pneumococcal rates are high (<87%). The PPV23 is part of the routine adult immunization schedule, but many adults are underimmunized [8]. In 2003, only 64% of adults 65 years of age or older had received the vaccine [97].

Pneumococcal vaccines 

A single dose of PPV23 should be given to persons 65 years of age or older or to persons 2 to 64 years of age with high-risk comorbidities. Children 2 to 4 years of age with indications for PPV23 should receive PPV23 at least 2 months after receiving doses of PCV7. Persons with an indication for PCV7 but with an uncertain vaccination history should receive one dose. A second dose of vaccine should be used for the following groups: (1) persons 65 years of age or older who received the vaccine at least 5 years before and were younger than 65 years of age at the time of initial vaccination; (2) persons with sickle cell disease, asplenia, renal disease, hematologic disease, malignancy, or HIV/AIDS; and (3) children younger than 10 years of age, in whom the second dose may be given 3 years or more after the first dose (Box 2) [98].

Severe reactions are rare with pneumococcal vaccination (PCV7 and PPV23). Adverse effects are mild and generally consist of transient localized reactions, such as erythema, swelling, and tenderness. Mild reactions occur in 10% to 23% of infants after PCV7 vaccination. In 1% to 9% of cases, larger regional areas of erythema and swelling may occur. Low-grade fever can occur in up to 24% of children after PCV7 vaccination. For PPV23 vaccination, mild transient local side effects occur in approximately 50% of patients and are more common after subsequent vaccinations. Systemic symptoms, including myalgias and fever, are rare after PPV23 vaccination [99].

Implementation of immunization programs in the emergency department 

Although the possible administration of influenza and pneumococcal immunization in the ED has been considered for more than 20 years, with the earliest report occurring in 1987 by Polis and colleagues [20], and many subsequent reports and organizations have recommended that these vaccines be administered in the ED, widespread use continues to be lacking. In a recent CDC publication that included the ACIP recommendations, it was reported that influenza immunizations have been administered successfully in outpatient facilities, managed care organizations, assisted living facilities, correctional facilities, pharmacies, and adult workplaces [42].

Administration of influenza vaccines in pharmacy-based supermarket chains was described by Weitzel and colleagues [100]; currently, these programs exist in several department store and supermarket chains. When surveyed, vaccinations in nontraditional setting, such as stores, community centers, and the workplace, were more likely for young healthy adults [101]. In another report, emergency medical services (EMS) personal immunized 2075 adults in a variety of locations, including EMS stations, churches, senior citizen complexes, and private residences [102]. In the recently published ACIP recommendations [43], standing orders to offer influenza vaccines to all hospitalized persons in acute care hospitals was recommended. The long-term care facilities have used standing orders programs for these vaccines, and it is recommended that such programs be conducted under the supervision of licensed practitioners so that patients can be appropriately screened, vaccines appropriately administered, and adverse events monitored. Although it is generally recommended that outpatient facilities, such as physicians' offices and a list of other specialty clinics, administer these immunizations, it was also recommended by the ACIP that outpatient facilities providing episodic acute care, such as EDs and walk-in care clinics, also administer these vaccines.

Payment for influenza and pneumococcal vaccines is available under Medicare Part B, and roster billing can be used. In EDs, there are many impediments to administering vaccines. Increasing patient volumes and overcrowding make it more difficult for ED personnel to take the time to screen for eligible patients. In many of the reported ED-based studies, additional nurses or research personnel were used for this purpose. Standing orders have been recommended, but ED personnel still are required for screening. The implementation of computerized order entry for admitted patients with mandatory immunization screening has helped to increase the rates of immunization for eligible hospitalized patients. As computerized chart documentation and order entry become more popular in the ED, such programs, coupled with standing orders, may help to increase administration rates of these vaccines. As with any medication or immunization administered in the ED, efforts to monitor safety and to inform patients' physicians should ideally become part of the program as well.

During a recent lecture by the primary author, a “top 10” list was provided regarding the rationale for implementing an ED-based influenza administration program. The 10 reasons are listed here in no particular order of importance (Box 3).