The following discussion of VPDs is not comprehensive. The pathogens associated with these 9 diseases were chosen as most relevant to anesthesiologists, intensivists, and other hospital-based clinicians based on their communicability, virulence, and epidemiologic importance. Most exhibit respiratory transmission and can cause severe cardiovascular, respiratory, or neurologic dysfunction. The clinical characteristics of the pathogens and the procedures and equipment necessary to care safely for infected patients are summarized in Figure 3 and Table 2.
Despite the introduction of an effective vaccine 50 years ago, measles continues to affect 20 million people a year worldwide, causing severe morbidity and mortality. Although measles was declared eliminated from the United States in 2000, continued importation of the virus from endemic areas into an increasingly undervaccinated population has led to its domestic reemergence (Supplemental Digital Content, Ref. 15, http://links.lww.com/AA/B367). Measles affects every major organ system and can lead to complications such as pneumonitis, tracheobronchitis, encephalitis, and death. Children with measles who are vitamin A deficient are prone to severe keratitis, corneal scarring, and blindness, making measles one of the leading acquired causes of blindness in the world.44 Complications from measles are much more likely in children younger than 5 years of age, older adults, and patients who are malnourished, immunocompromised, or have poor access to medical care (Supplemental Digital Content, Ref. 16, http://links.lww.com/AA/B367).19 Measles infection during pregnancy is also associated with severe complications such as pneumonitis and adverse fetal outcomes such as stillbirth or spontaneous abortion.45 Although many of the life-threatening complications of measles can be successfully treated, the direct and indirect costs are high.
The measles virus is a paramyxovirus transmitted through contact with respiratory droplets or aerosols spread by coughing or sneezing. It is one of the most easily transmittable pathogens known and can persist on surfaces or in the air up to 2 hours after leaving its host. It is so contagious that up to 90% of unvaccinated people in face-to-face contact with a sick patient become infected themselves (Supplemental Digital Content, Ref. 17, http://links.lww.com/AA/B367). Many outbreaks in the United States and Europe over the past 3 decades have demonstrated that large numbers of people may be rapidly infected even when not in close contact with the index case.46–48 Within the past 5 years, cases of measles in the United States have been linked to large outbreaks in France in 2010 to 2011 and in the Philippines in 2014. Measles remains endemic in many countries in the Western Pacific region, and measles outbreaks involving tens of thousands of people have continued to occur across Europe in the past decade (Supplemental Digital Content, Refs. 13 and 18, http://links.lww.com/AA/B367).41
The measles virus targets epithelial cells, reticuloendothelial cells, and leukocytes. Immune system function is depressed for months and possibly years because of measles infection, leading to an increased chance of secondary infection.44,49 After exposure and an average incubation period of approximately 10 days, nonspecific symptoms of fever, cough, coryza, and conjunctivitis appear, followed by a characteristic truncal and facial rash 2 to 4 days later. Patients can be infectious before the appearance of the rash. Malaise, photophobia, sore throat, headache, and generalized lymphadenopathy are also common. Most healthy patients recover within 2 weeks.44
Severe complications are more likely to occur in young children, older adults, and immunocompromised patients. Measles case fatality rates for patients with cancer or HIV are 40% to 70%.50 Dehydration, diarrhea, and otitis media are common in patients hospitalized for measles, with the latter sometimes leading to permanent deafness. The leading cause of death from measles is pneumonitis, which is present in the majority of patients hospitalized with measles. Pneumonitis develops in approximately 1 in 20 children with measles, with a similar incidence in adults (Supplemental Digital Content, Ref. 19, http://links.lww.com/AA/B367).51 Pneumonitis can be caused by the measles virus alone, by a secondary viral infection, or by a secondary bacterial infection (e.g., Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae). In adults, measles pneumonitis in critically ill patients is associated with extraalveolar air leak complications such as pneumothorax and/or pneumomediastium.52 The second most common cause of death in children hospitalized with measles in the United States is laryngotracheobronchitis (croup). Secondary viral and bacterial infections of airway structures are also possible, and diffuse airway inflammation, airway obstruction, and respiratory distress may necessitate intubation and mechanical ventilation.44 In addition to supportive care, supplemental vitamin A should be given to children younger than 2 years with severe measles to reduce mortality.44
Measles infection can cause devastating neurologic complications. Approximately 1 to 3 of 1000 persons with measles will develop measles encephalitis. This manifestation is more likely in adolescents and adults than young children. Encephalitis presents with the abrupt onset of fever, seizures, altered mental status, and focal neurologic changes, and it is associated with a mortality rate of 10% to 15%. Survivors may experience severe and permanent neurologic sequelae including blindness and neurocognitive dysfunction. Measles encephalitis in patients with HIV or leukemia is usually fatal. Prevention of encephalitis is perhaps the most compelling argument for universal measles vaccination, because other measles-related complications are rarely life threatening with modern medical care. Very rarely, the persistence of measles virus in the central nervous system (CNS) can cause subacute sclerosing panencephalitis, a slowly progressive demyelinating disease that can lead to myoclonus, seizures, coma, and death.44,53
The live attenuated measles vaccine, given as a part of the MMR vaccine, is approximately 95% effective in preventing measles infection after 1 dose and 99% after 2 doses. Most adults born in the United States assume they are immune. However, the inactivated (killed) measles vaccine given in the United States between 1963 and 1967 and through the 1970s in other countries does not have the same efficacy as the live vaccine, and individuals who received this vaccine are at risk for an atypical presentation of measles, characterized by hypersensitivity polyserositis, fever, pneumonia, pleural effusions, and peripheral edema.19,54 Even those individuals born before 1957 who are presumed to have experienced a measles infection in childhood may not be immune. Serologic studies on US hospital personnel born before 1957 have found that 5% to 9% have no detectable measles antibody.19 The median rate of measles seronegativity in HCP of any age in North and South America is 5.8% (range, 3.1%–8.4%), and HCP younger than 30 years are particularly vulnerable.55
From the perspective of the anesthesiologist and critical care physician, the clinical significance of measles is 2-fold. First, patients hospitalized with measles are most likely to die of respiratory complications. Thus, tracheal intubation and extended mechanical ventilatory support can be anticipated. Second, the virus spreads with stunning efficiency in enclosed spaces such as schools, dormitories, and hospitals. Patients admitted with suspected measles should be kept in respiratory isolation with airborne and contact transmission precautions (Fig. 3). Although the majority of adults in the United States are immune to measles, some are not, and the immunocompromised status of some hospitalized patients puts them at risk for death and devastating complications from nosocomial infection. The first confirmed measles death in the United States since 2003 occurred in 2015 in the state of Washington. The patient, who died of measles pneumonitis, was immunocompromised and most likely exposed to measles at a local medical facility (Supplemental Digital Content, Ref. 20, http://links.lww.com/AA/B367).
The incidence of mumps has decreased dramatically since the mumps vaccine was licensed in 1967, reaching a nadir in 2003 after a second dose of the MMR vaccine was recommended in 1989.19 Nonetheless, mumps outbreaks that primarily affect college students continue to occur in the United States. In 2006, a multistate mumps outbreak in Midwest college campuses involved 6584 cases and resulted in 85 hospitalizations.56 Since 2010, approximately 200 to 2600 mumps cases have occurred in the United States annually (Supplemental Digital Content, Ref. 21, http://links.lww.com/AA/B367). Although the mumps component of the MMR vaccine is approximately 88% effective after 2 doses, outbreaks can still occur in highly vaccinated communities, particularly in close-contact settings such as dormitories. The estimated herd immunity threshold for mumps ranges from 88% to 92%, requiring a 95% vaccination rate by conservative measures.57,58 The duration of protection from this vaccine is approximately 10 to 15 years.59,60
Mumps is caused by a paramyxovirus transmitted through respiratory droplets. The incubation period ranges from 2 to 4 weeks, and the infection is completely asymptomatic in one-third of cases. Symptoms usually include fever, headache, fatigue, and sometimes arthralgia. The pathognomonic feature of mumps is inflammation of the parotid glands, although other salivary glands are involved 10% of the time. Mumps can also affect a wide range of organ systems, leading to complications such as epididymo-orchitis, aseptic meningitis, pancreatitis, transient deafness, and rarely encephalitis.61–63 In pregnant women during the first 12 weeks of gestation, mumps is particularly teratogenic and results in a 25% spontaneous abortion rate.64 Although it is very rare that anyone who contracts mumps will die of the infection, mumps-associated complications increase medical costs and impact maternal–fetal health. Droplet precautions should be used when caring for patients with mumps, and no pregnant HCP should be involved in their care (Fig. 3).
Rubella, also known as German measles or “3-day measles,” is caused by an RNA virus of the family Togaviridae. The rubella virus is transmitted by respiratory droplets. It is frequently spread by infected individuals with very mild symptoms or no symptoms at all. After a 12- to 23-day incubation period, the virus replicates in the nasopharynx and regional lymph nodes and then disseminates throughout the body. Infection with rubella virus can also occur in utero, which may lead to congenital rubella syndrome (CRS).19,65
Rubella is a mild and self-limited disease in most cases, especially in children. Symptoms include low-grade fever, nausea, mild conjunctivitis, and, in 50% to 80% of cases, a characteristic maculopapular rash. The rash typically starts on the face and neck before involving the rest of the body and lasts for 1 to 3 days. Lymphadenopathy behind the ears and on the neck can also be seen. Arthralgia and arthritis affecting hands, wrists, and knees may occur in up to 70% of young female adults but rarely in adult males or children. Joint symptoms may last for several weeks and rarely lead to chronic arthritis. Encephalitis and hemorrhagic manifestations are rare, occurring in 1 in 6000 cases and 1 in 3000 cases, respectively.19 Myocarditis associated with rubella infection has been reported.66 Treatment for rubella is primarily supportive.
In contrast, congenital rubella infection has dire consequences. Maternal infection, particularly during the first trimester, can lead to miscarriage, stillbirth, and severe birth defects including deafness, cataracts, microcephaly, severe cognitive delay, complex congenital heart disease, thrombocytopenia, purpura, hepatosplenomegaly, pneumonitis, and radiolucent bone disease (Supplemental Digital Content, Ref. 22, http://links.lww.com/AA/B367).67,68 Infants with CRS shed virus from body secretions for up to a year and may infect susceptible individuals in close contact with them.19 Despite large-scale public heath campaigns, an estimated 100,000 cases of CRS still occur annually worldwide.69
Since the introduction of a rubella vaccine in 1969, the incidence of rubella has declined precipitously, and endemic rubella was declared eliminated in the United States in 2004 (Supplemental Digital Content, Ref. 22, http://links.lww.com/AA/B367). However, many other countries lack strong rubella immunization and reporting programs, and there is a continuing risk of rubella importation into the United States. In addition to rubella outbreaks in the developing world, large recent epidemics have occurred in Poland (38,851 cases in 2013), Romania (11,809 cases in 2012), and Japan (10,102 cases in 2013), all linked to low rubella vaccination rates (Supplemental Digital Content, Refs. 23 and 24, http://links.lww.com/AA/B367).70 The 3 CRS cases most recently reported in the United States in 2012 were infants whose unvaccinated mothers had travelled to rubella-endemic countries.71
For anesthesiologists and intensivists, severe rubella disease is most likely to be encountered in neonates. Any infant with CRS being considered for surgery should undergo thorough preoperative cardiac evaluation including transthoracic echocardiography to evaluate for potential congenital heart disease. Cleft palate and micrognathia may complicate airway management.72 Prolonged postoperative respiratory depression associated with central hypoventilation has been described in infants and adults with CRS undergoing anesthesia.73 Overall, the major concern in caring for a hospitalized patient with rubella is preventing disease transmission to susceptible individuals. Pregnant HCP should not care for rubella-infected patients (Supplemental Digital Content, Refs. 22 and 25 http://links.lww.com/AA/B367).
Pertussis is an acute respiratory illness that occurs year-round with epidemic cycles every 3 to 5 years. The incidence of pertussis in the United States has been increasing steadily for 2 decades (Fig. 1). In 2012, 48,277 cases were reported in the United States, more than any year since 1955 (Supplemental Digital Content, Ref. 26, http://links.lww.com/AA/B367). In California, 2 pertussis epidemics since 2009 have sickened nearly 20,000 patients and caused at least 1100 hospitalizations and 13 infant deaths.74 It is a severely underreported disease, with an estimated one-third of cases captured by public health agencies.75
Pertussis is caused by Bordetella pertussis, a small Gram-negative rod. The organism is transmitted primarily through respiratory droplets, and it binds to and damages respiratory epithelium through the release of several cytotoxins. It is a highly contagious pathogen that is notoriously difficult to diagnose. After a 4- to 21-day incubation period in which an infected individual is asymptomatic but still infectious, pertussis infection progresses through 3 stages of illness: “catarrhal,” “paroxysmal,” and “convalescent.” The catarrhal stage is largely indistinguishable from common viral upper respiratory tract infections with cough, rhinorrhea, and malaise. Unlike such infections that improve after 1 to 2 weeks, pertussis progresses to the paroxysmal stage. The hallmark of the paroxysmal stage is sudden, severe coughing fits. Violent exhalation followed by forceful inhalation leads to a characteristic “whooping” sound. These coughing fits last approximately 1 to 2 months, are often worse at night, and may be accompanied by posttussive emesis. During the convalescent phase, cough frequency decreases, and symptoms gradually resolve over the subsequent month. The mainstay of treatment is a short course of a macrolide antibiotic or trimethoprim/sulfamethoxazole, although this is often given too late to affect the course of illness. Despite antibiotic therapy, a cough may persist for weeks.75,76
Severe complications of pertussis cause hundreds of thousands of deaths in infants worldwide every year. Approximately half of infants who get pertussis in the United States are hospitalized. Of those, 67% have apneic episodes, 23% develop pneumonia, 1.6% have seizures, and 1.6% die. Encephalopathy occurs in 0.4% of patients and may be because of pertussis toxin or because of severe hypoxia caused by coughing fits. In adolescents and adults, the disease is milder, with a hospitalization rate <3%. Forceful coughing fits can lead to dehydration and weight loss and can rarely lead to rib fractures, pneumothorax, syncope, intracranial hemorrhage, vertebral and carotid artery dissections, coronary ischemia, hernia, or hearing loss (Supplemental Digital Content, Ref. 27, http://links.lww.com/AA/B367).75,77
The original pertussis vaccine introduced in the 1940s was made from a suspension of formalin-inactivated B pertussis cells. This “whole cell” vaccine was effective but was associated with a high rate of adverse events including fever, pain, and swelling at the injection site. Concerns about safety led to the introduction of purified acellular pertussis vaccines in the 1990s that were associated with fewer adverse effects. Two types of acellular pertussis vaccines are available and both are combined with vaccines for diphtheria and tetanus. The DTaP vaccine is given to infants and has a higher dose of diphtheria toxoid and acellular pertussis components (as reflected by name capitalization) compared with the Tetanus-diphtheria-acellular pertussis (Tdap) vaccine, which is given as a booster for adolescents and adults. Current recommendations are that adults aged 19 to 65 years receive the Tdap vaccine once and also during every pregnancy (Supplemental Digital Content, Ref. 1, http://links.lww.com/AA/B367).78
Reimmunization is necessary for adolescents and adults because immunity wanes rapidly after administration of acellular pertussis vaccines.74 In 1 study, only 10% of children remain protected 8.5 years after the last DTaP dose.79 In addition to waning immunity, cases of “vaccine failure” may also be attributable to an increased awareness and reporting of the disease and to genetic mutations in B pertussis.79–81 For these reasons, the incidence of pertussis is increasing in adolescents and adults, in whom illness is often mild and frequently not diagnosed.75 In fact, pertussis may be responsible for 12% to 32% of prolonged cough illnesses in this population.75,77,82 Furthermore, in one 2008 study, 90% of HCP showed an increase in antibodies to 1 or more pertussis antigens during a 5-year period, suggesting a high rate of unrecognized pertussis infection in health care settings.83 Because adults are the primary source of infection for the majority of infants infected with pertussis, maintenance of herd immunity is crucial to safeguard the infant population that is too young to be protected by vaccination.84 Disturbingly, Tdap vaccination rates in some adult populations in the United States are as low as 10% and in HCP only 27%.85,86 HCP should stay current with Tdap vaccination recommendations and use droplet precautions when caring for patients with suspected pertussis. HCP exposed to pertussis, regardless of immunization status, sometimes require postexposure antibiotic prophylaxis to prevent nosocomial transmission (Table 3).
Although the incidence of diphtheria has been dramatically reduced by vaccination, its case fatality rate of 5% to 10% (and up to 20% in some cases) has changed very little in the past 50 years (Supplemental Digital Content, Ref. 28, http://links.lww.com/AA/B367). The DTaP vaccine is estimated to be 89% effective at preventing diphtheria after a single dose and 98% after 4 or more doses.89 However, the vaccine’s duration is only about 10 years, requiring a subsequent booster injection after the initial DTaP series is completed. In recent history, the largest epidemic of diphtheria occurred in the Newly Independent States of the former Soviet Union between 1990 and 1996, in which >140,000 people were infected and 4000 died. Several factors contributed to this epidemic, including the emergence of a new bacterial subtype, public suspicion of the Soviet government’s childhood vaccination program, and spread of the illness through unvaccinated military personnel and refugees from multiple civil wars in Central Asia.90
Diphtheria is caused by the bacterium Corynebacterium diphtheriae and other Corynebacterium species and is usually transmitted through respiratory droplets or through mucous membrane contact with respiratory secretions.91 The incubation period is approximately 2 to 5 days, and the disease itself can involve nearly any mucous membrane. Early symptoms of diphtheria include fever, fatigue, sore throat, and anorexia. C diphtheriae tends to localize to the upper respiratory tract, ulcerating mucosa and inducing the formation of a pathognomonic inflammatory pseudomembrane on the pharynx, tonsils, and nasal membranes.92 Any manipulation of the pseudomembrane can cause bleeding, and extensive pseudomembrane formation may cause airway obstruction. Associated cervical lymphadenopathy and soft tissue edema often result in a characteristic “bull neck” appearance and may contribute to airway compromise. The infection can spread directly to the esophagus, larynx, and tracheobronchial tree, leading to pneumonia and eventually bronchial obstruction from suppurative inflammation.93,94 Furthermore, bacterial exotoxin is absorbed into the bloodstream and can inhibit cellular protein synthesis. Toxin-mediated myocarditis results in conduction abnormalities and ventricular failure and is associated with a very high mortality rate.95 Toxin-mediated neuritis usually affects motor neurons and is self-limited. Paralysis of oculomotor muscles, laryngeal muscles, distal extremities, or the diaphragm may occur depending on duration and severity of the infection. About 20% of all diphtherial respiratory infections are followed by some form of neuritis.19,92 Treatment of diphtheria involves the timely use of diphtheria antitoxin, which neutralizes the effects of the circulating exotoxin. Ideally, antitoxin should be given within the first week of symptom onset. Antibiotics, usually penicillin or erythromycin, are recommended for the patient and for close contacts who may have been exposed (Supplemental Digital Content, Ref. 28, http://links.lww.com/AA/B367).
Several aspects of diphtheria infection are relevant to anesthesiologists and intensivists. Respiratory compromise necessitating tracheal intubation and mechanical ventilation may occur from either airway obstruction or respiratory failure from pneumonia or phrenic nerve dysfunction. The clinical presentation of diphtheria can mimic other airway emergencies such as epiglottitis, peritonsillar abscess, or angioedema.91,96,97 Edema and bleeding from manipulation of the friable pharyngeal pseudomembrane can make airway management challenging. Tracheostomy and direct laryngoscopy have been used successfully to secure the airway in patients with diphtheria, although details of airway management are not provided in case reports.91,94,96–99 The choice of intubation technique (direct laryngoscopy, videolaryngoscopy, or fiberoptic bronchoscopy) should be left to the discretion of the clinician based on experience and available equipment. Any attempt at intubation should be made with an otolaryngologist at bedside prepared to perform a surgical airway immediately.98 Finally, severe cardiac depression and dysrhythmia from myocarditis are also consequences of advanced illness.19,95 Transthoracic echocardiography (rather than transesophageal, which may cause trauma to the pseudomembrane-covered oropharynx) to evaluate ventricular function should be considered for any patient admitted with diphtheria.
Meningococcus (Neisseria meningitidis) is an encapsulated Gram-negative diplococcal bacterium that colonizes the mucosa of the human nasopharynx in 10% of the population.100 This organism exhibits respiratory droplet transmission, and clinical infection can present in many forms including meningitis, pneumonia, septic arthritis, and bacteremia. Acute life-threatening complications of meningococcal disease include septic shock, coagulopathy, and epiglottitis. Although the incidence of meningococcal disease is low, 10% to 15% of cases are fatal, and up to 20% of survivors have permanent hearing loss, brain injury, or other serious complications. Those at the greatest risk of invasive infections are infants, adolescents, young adults living in college dormitories and military barracks, and asplenic and complement-deficient patients of all ages.101–104
The incidence of invasive meningococcal infection in the United States has been steadily declining since 1990, after multiple vaccines were licensed in the 1970s and 1980s and refined in the following 2 decades.19 Vaccination against meningococcus confers not only biological immunity, but also herd immunity by reducing the carrier rate of the microorganism in the population.26,101,105 Worldwide, meningococcal disease continues to be a significant problem. Large epidemics occur in sub-Saharan Africa every 5 to 10 years and affect hundreds of thousands of people (Supplemental Digital Content, Ref. 29, http://links.lww.com/AA/B367).
Anesthesiologists and intensivists should know that severe meningococcal disease usually manifests in 1 of 2 forms: meningitis or fulminant meningococcal sepsis (FMS). These presentations may occur separately or overlap. In meningitis, the sudden onset of chills, fever, low-back pain, and myalgia rapidly progresses to typical signs and symptoms of bacterial meningitis and cerebral edema. In FMS, release of bacterial endotoxin causes an overwhelming host cytokine response and severe septic shock. FMS is associated with disseminated intravascular coagulation, characteristic skin hemorrhage, and severe cardiac depression. The mortality rate of FMS varies from 20% to 80% in different studies and depends on how FMS is defined and variation in the natural course of the disease.106 Clinical deterioration is overwhelming, and approximately half of patients with FMS die within 24 hours of symptom onset, even with prompt treatment. Many of those who die will do so before arrival at the hospital.106 Antibiotics and aggressive management of septic shock and multiorgan failure in the intensive care unit are the cornerstones of treatment. Prevention of meningococcal disease by vaccination and droplet transmission precautions in the hospital is preferable (Supplemental Digital Content, Ref. 25, http://links.lww.com/AA/B367).106
Influenza (“flu”) viruses are responsible for seasonal influenza epidemics that cause 3 to 5 million cases of severe illness and 250,000 to 500,000 deaths annually worldwide. They are also responsible for worldwide pandemics that have killed millions (Supplemental Digital Content, Ref. 30, http://links.lww.com/AA/B367).107 Unlike some of the other pathogens discussed, the influenza virus has never been close to elimination in human populations, persisting in human and animal reservoirs and constantly changing. Understanding the threat posed by influenza viruses means that clinicians must not only understand the pathophysiology of the disease but they must also understand how seasonal influenza differs from pandemic influenza in scope and severity.
Influenza viruses belong to the Orthomyxoviridae family and are classified into types A, B, or C based on the antigenic differences in their nucleoproteins and matrix proteins. Influenza type A and B viruses cause seasonal epidemics of disease, whereas influenza type C viruses cause a mild respiratory illness. Influenza type A viruses are further classified based on their expression of 2 surface glycoproteins: hemagglutinin (H) and neuraminidase (N). There are 18 different hemagglutinin subtypes (H1 through H18) and 11 different neuraminidase subtypes (N1 through N11) identified to date. Currently, the subtypes of influenza A viruses active in humans are H1N1 and H3N2 (Supplemental Digital Content, Ref. 31, http://links.lww.com/AA/B367). Influenza type A viruses are found in many animals, including humans, pigs, and birds. Pigs, which also express receptors for avian and human viruses, are ideal hosts for the genetic mixing of avian, porcine, and human forms of influenza. Through a process termed “antigenic drift,” reassortment of genes in human, swine, and avian viruses constantly changes the antigenic characteristics of the hemagglutinin and neuraminidase glycoproteins expressed on influenza viruses.108 The composition of the influenza vaccine must thus be adjusted annually to include the most recent and virulent circulating strains of influenza A (H1N1), A (H3N2), and 1 or 2 influenza B viruses.19 Efficacy of the annual vaccine depends, among other factors, on how well the vaccine matches currently circulating viral strains. Influenza A viruses that have undergone more profound antigenic shifts than usual become novel strains and are responsible for periodic influenza pandemics. During pandemics, which are discussed further below, influenza infections can exhibit strikingly different patterns of morbidity and mortality, and available vaccines may not prevent infection.
Influenza viruses are spread predominantly through respiratory droplets and mucous membrane contact with secretions. Airborne transmission through aerosols may also be an important mechanism.109 Systemic influenza infection is characterized by the sudden onset of high fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis. Gastrointestinal symptoms including vomiting and diarrhea can occur. Most people recover in 1 to 2 weeks and do not require any medical treatment (Supplemental Digital Content, Ref. 32, http://links.lww.com/AA/B367). However, in the very young, the elderly, pregnant women, and people with chronic medical conditions, influenza can lead to serious complications and death. In the United States, 225,000 people are hospitalized, and about 36,000 deaths occur annually because of seasonal influenza, primarily in people older than 65 years.110,111 The most frequent serious complications of influenza are pulmonary, with viral pneumonitis and secondary bacterial pneumonia the most prominent. Influenza pneumonitis is increasingly recognized as an important cause of severe community-acquired pneumonia in both children and adults.112 Hemagglutinin molecules on influenza viruses bind to sialic acid molecules expressed by ciliated columnar epithelial cells in the respiratory epithelium. Respiratory epithelial cells are invaded, viral replication occurs, and ultimately host cell death results. Different subtypes of the sialic acid molecule are expressed in upper and lower respiratory tract epithelium, and the affinity of a particular hemagglutinin to each may determine whether a strain of influenza causes a milder upper respiratory tract infection (seasonal influenza) or severe pulmonary involvement (pandemic H1N1, avian influenza).107,113 Secondary infections with S aureus, S pneumoniae, and H influenzae are common, particularly in the setting of influenza pandemics. The bacteria appear to work synergistically with the virus to establish infection, enhance viral replication, and alter the host immune response. The 1918 “Spanish Flu” pandemic (discussed below) was notable for the remarkably high incidence of S aureus pneumonia after viral infection, clearly one reason for the high mortality associated with this pandemic.
Other complications of severe seasonal influenza are uncommon. CNS involvement may present as encephalopathy (Reye syndrome), encephalomyelitis, transverse myelitis, meningitis, or GBS. Cardiac complications usually arise from exacerbation of underlying cardiac disease, although pericarditis and myocarditis have been described. Abnormal electrocardiographic findings have been described in 50% of adults with influenza without cardiac symptoms. Viral effects on skeletal muscle rarely can cause myositis and rhabdomyolysis leading to renal failure.110
Influenza pandemics are associated with higher morbidity and mortality compared with seasonal epidemics. Four major influenza pandemics have occurred during the past century: Spanish influenza (H1N1) 1918 to 1919, Asian influenza (H2N2) 1957 to 1958, Hong Kong influenza 1968 to 1970, and swine-origin A (H1N1) 2009. Of these, the 1918 Spanish influenza pandemic was the most devastating, infecting one-third of the world’s population and killing approximately 40 to 100 million people. The 1918 H1N1 virus was unusually virulent, with a case fatality rate about 2.5% in the United States, compared with <0.1% in other influenza pandemics. In addition, at least 50% of deaths were in an unusually young age group: 20 to 40 year olds. All influenza pandemics since 1918 have been caused by descendants of the 1918 virus in which novel avian influenza genes have been incorporated.107,114 The most recent pandemic was caused by a swine-origin influenza “Pandemic A H1N1” (pH1N1) virus that emerged in Mexico in April 2009. It spread rapidly, ultimately infecting an estimated 25% of the world’s population and 50% of school-aged children.115 Fortunately, in most individuals, the pH1N1 strain caused a mild, self-limiting upper respiratory tract illness, and progression to severe disease was rare, with a US case fatality rate of only 0.08%. Even so, approximately 60 million cases, 274,304 hospitalizations, and 12,469 deaths were associated with pH1N1 in the United States between 2009 and 2010.116 Patients hospitalized with pH1N1 were more likely to be young adults who were previously healthy, in stark contrast to the frailer patients most at risk for seasonal influenza complications. Hospitalized pH1N1 patients were also typically critically ill, required prolonged mechanical ventilation, and had poor outcomes. Patients died of fulminant viral pneumonitis, acute respiratory distress syndrome, septic shock, and multiorgan failure, and overall hospital mortality was a staggering 11% to 56%.113,117–120 The major risk factors predictive of mortality were pregnancy and, for unclear reasons, obesity.121 pH1N1 required the development and distribution of a completely different influenza vaccine than was already in production at the start of the outbreak, a process that took 6 months (Supplemental Digital Content, Ref. 33, http://links.lww.com/AA/B367).
Antiviral medications play an important role in treating severe influenza infections. The older antiviral medications amantadine and rimantadine are less expensive and are effective both for prophylaxis and for reducing the severity of ongoing infection. However, they are only effective against some strains of influenza A, and severe side effects such as delirium and seizures may develop in the elderly. Newer antiviral medications called neuraminidase inhibitors (zanamivir and oseltamivir) are effective against the majority of influenza strains and have fewer adverse effects than amantadine and rimantadine. However, neuraminidase inhibitors are expensive and are not available in many countries. Treatment for severe influenza consists of supportive care, including hospital admission, intensive care, mechanical ventilation, antiviral therapy, and antibiotic therapy for secondary bacterial infection when indicated (Supplemental Digital Content, Ref. 30, http://links.lww.com/AA/B367). Extracorporeal membrane oxygenation may be an effective salvage treatment for patients with refractory respiratory failure attributable to influenza-related acute respiratory distress syndrome.120
The CDC recommends 3 interventions to limit the spread of influenza: avoiding close contact with sick people and washing hands often, taking flu antiviral drugs when prescribed, and getting vaccinated (Supplemental Digital Content, Ref. 34, http://links.lww.com/AA/B367). In the United States, vaccination during the 2013 to 2014 season resulted in an estimated 7.2 million fewer cases of influenza, 90,000 fewer hospitalizations, and 3.1 million fewer medically attended cases.122 Although the efficacy of the flu vaccine in preventing influenza and medical visits associated with influenza ranges from 10% to 60% depending on the year, there is evidence that vaccination substantially reduces the incidence of severe disease and rates of hospitalization in both children and adults (Supplemental Digital Content, Refs. 35 and 36, http://links.lww.com/AA/B367).123–125 Because of declining immune system function with age (“immunosenescence”126,127), efficacy of the vaccine also depends on patient age. Greatest efficacy is seen in children aged 6 months to 7 years, good efficacy is seen in older children and adults younger than 65 years, and modest to equivocal efficacy is demonstrated in adults aged 65 years and older.123,128 Thus, because influenza vaccine efficacy in the elderly is reduced, the protection afforded by herd immunity becomes even more important. Limiting influenza transmission by vaccinating young people decreases mortality from pneumonia and influenza in the overall population.129 Despite the limitations of influenza vaccination in the elderly, currently licensed vaccines in this patient population are still about 30% to 50% effective in preventing complications from influenza and all-cause mortality during the winter months.126 Vaccination against influenza also has substantial benefits for healthy working adults aged 18 to 64 years, which describes most HCP. Immunization in HCP decreases their frequency of upper respiratory tract infections by 25% and reduces both absenteeism from work and visits to outpatient clinics because of upper respiratory tract infection by 30% to 40%.33,130
The CDC and US Department of Health and Human Services recommend that clinicians use contact and droplet precautions including surgical masks during routine care of patients with seasonal and pandemic influenza (Supplemental Digital Content, Refs. 25 and 37, http://links.lww.com/AA/B367). When influenza-infected patients undergo aerosol-generating procedures (AGPs), such as tracheal intubation or bronchoscopy, the CDC further suggests that HCP consider using airborne precautions (including powered air-purifying respirators and N95 respirators) “tak[ing] feasibility into account, especially in challenging emergent situations, where timeliness in performing a procedure can be critical to achieving a good patient outcome” (Supplemental Digital Content, Ref. 38, http://links.lww.com/AA/B367). Severity of influenza infection is not mentioned as a criterion of whether airborne precautions should be applied, although those patients undergoing AGPs are presumably severely ill. The WHO recommends that HCP use respirators during AGPs performed on patients infected with any type of influenza (seasonal, pandemic, avian) or, for that matter, any other acute respiratory illness with epidemic or pandemic potential (Supplemental Digital Content, Ref. 48, http://links.lww.com/AA/B367). Given recent evidence that that airborne transmission of aerosolized influenza viruses can occur even in the absence of AGPs, HCP should also consider using airborne and contact precautions for all patient care during an influenza pandemic.109 Postexposure prophylaxis with oseltamivir is indicated for nonimmunized HCP exposed to influenza (Table 3).
Chickenpox (varicella) is a highly contagious disease caused by the varicella zoster virus (VZV), a DNA herpesvirus. Varicella occurs worldwide with a peak incidence in preschool and school-aged children. Data suggest that, since introduction of the varicella vaccine in 1995, the incidence of chickenpox has decreased significantly. However, varicella is not a reportable illness in the United States, so the true incidence of disease is unknown. The vaccine is 70% to 90% effective at preventing varicella, and >95% effective at preventing severe varicella disease.19 The virus is transmitted by respiratory droplets, aerosols, and direct contact with viral particles contained within skin blisters. After causing the systemic infection called chickenpox, varicella remains latent in dorsal root ganglia and can be reactivated later in life, resulting in herpes zoster (shingles). Like measles, varicella is highly contagious, with about 90% of susceptible close contacts developing disease after exposure. The asymptomatic incubation period is 10 to 21 days. Individuals with chickenpox are contagious 1 to 2 days before the appearance of a rash until all blisters have developed into scabs (Supplemental Digital Content, Ref. 39, http://links.lww.com/AA/B367). Adults typically present with a prodrome of malaise, headache, and fever, which generally precedes a characteristic pruritic rash by 1 to 2 days. The rash affects the face and trunk first and then the extremities. Skin lesions progress rapidly from macules to papules to vesicles. The clinical course in healthy children is similar, but generally milder and associated with fewer complications than in adults. After primary varicella infection, herpes zoster can result from reactivation of latent VZV in spinal and cranial sensory ganglia and is associated with a painful, contagious vesicular rash.19
Severe complications of varicella include bacterial superinfection of skin lesions, pneumonitis, encephalitis, meningitis, thrombocytopenia, glomerulonephritis, and myocarditis. Infection during pregnancy is associated with severe illnesses such as pneumonitis or encephalitis in the mother and congenital varicella syndrome and severe disseminated infection in the neonate.131,132 Compared with children, adolescents and adults have a 10- to 20-fold increased risk of death and complications from varicella infection.19 Varicella pneumonitis is the most common complication and reason for hospitalization among adults infected with chickenpox. Particularly at-risk adult populations include smokers, the immunocompromised, pregnant women, and those with chronic lung disease.133,134 Symptoms of pneumonitis typically manifest in the first week after rash development and include tachypnea, cough, dyspnea, chest pain, and rarely hemoptysis. Chest radiograph abnormalities are apparent in as many as 16% of those infected with chickenpox, suggesting that an asymptomatic viral pneumonitis is also common.135 Limited data suggest that early therapy with IV acyclovir probably reduces varicella pneumonitis-related morbidity and mortality.133 Historically, mortality from varicella pneumonitis was estimated between 10% and 40%. With early antiviral therapy and modern intensive care, the mortality rate now approaches 0, even in pregnant women.136,137
Varicella infection may also cause neurologic complications. Symptomatic cerebellar ataxia occurs in approximately 1 in 4000 varicella cases. Headache, vomiting, lethargy, and occasionally nystagmus and nuchal rigidity accompany ataxia, and these symptoms usually present concurrently with a rash. In most patients, symptoms are self-limited and resolve without sequelae in 1 to 3weeks. In contrast, varicella encephalitis, which occurs in 1 in 5000 to 10,000 cases, can be devastating. Adults and infants are most at risk for encephalitis, which presents with headache, vomiting, fever, and altered mental status about 1 week after the onset of a rash. Seizures are common, and focal neurologic deficits are sometimes observed. The mortality rate is 5% to 10%, and although most patients recover completely, 10% to 20% of survivors experience long-term sequelae including seizure disorders. IV acyclovir is indicated for the treatment of both varicella cerebellar ataxia and encephalitis.138
Of all VPDs, poliomyelitis (polio) has been the most feared in modern times. Repeated polio epidemics in the 20th century killed thousands of people and left millions with permanent paralysis and disability. These terrifying epidemics drove extraordinary advances in public health and medicine, including the development of the first polio vaccine by Jonas Salk in 1952, implementation of widespread vaccination programs worldwide, creation of the specialty of intensive care by Danish anesthesiologist Bjørn Ibsen, and invention of the “iron lung.”139,140 Although poliovirus has been eliminated from the Americas for many years, an estimated 20% of the world’s population lives in areas where wild poliovirus still persists (Supplemental Digital Content, Ref. 40, http://links.lww.com/AA/B367). Beginning in 1988, the WHO embarked on a global effort to eradicate poliomyelitis that has been largely, although not completely, successful. The disease remains endemic in Afghanistan and Pakistan, and until recently, Nigeria (Supplemental Digital Content, Ref. 41, http://links.lww.com/AA/B367).141 Eradication efforts in these countries have been impeded by local suspicions that the United States and the United Nations are using vaccination programs to sterilize children or infect the population with HIV (Supplemental Digital Content, Ref. 42, http://links.lww.com/AA/B367).142 Polio vaccination programs were further undermined by a report in 2011 that the US Central Intelligence Agency had attempted to collect blood samples from relatives of Osama bin Laden under the guise of a hepatitis B vaccination program in Pakistan.143 Since 2012, Taliban leaders have banned all vaccination programs in areas under their control and have called for the assassination of HCP administering vaccinations.144 In addition to areas endemic for polio, outbreaks have surfaced in China in 2011,145 in Syria in 2013,146 and the Ukraine in 2015 (Supplemental Digital Content, Ref. 43, http://links.lww.com/AA/B367). Thus, poliomyelitis continues to be a threat for unvaccinated individuals.
Poliovirus is an RNA virus of the genus Enterovirus, which colonizes the human oropharynx and gastrointestinal tract. Of the 3 serotypes of poliovirus (PV1, PV2, and PV3), the PV1 serotype is most commonly associated with paralysis.147 Vaccination or exposure to all 3 serotypes, however, is necessary to convey immunity. Two polio vaccines are available worldwide: the inactivated poliovirus vaccine (IPV) and the attenuated live oral poliovirus vaccine. The oral poliovirus vaccine is inexpensive, easy to administer, and has become the vaccine of choice in endemic areas. However, it carries a rare risk of paralytic polio (about 1 in 750,000). For this reason, only the IPV, which does not carry the same risk of paralytic disease, is used in the United States and Canada (Supplemental Digital Content, Ref. 44, http://links.lww.com/AA/B367).148 Three doses of the IPV produce immunity in about 99% of recipients. Immunity is long lived, with 99% of recipients protected for at least 18 years. Reimmunization is recommended for those traveling to endemic areas.19
Poliovirus is transmitted through fecal-oral and oral-oral routes, and it may be shed by infected individuals for several weeks after infection.149 Poliovirus is highly contagious, with a 90% to 100% seroconversion rate in susceptible household contacts. The virus initially gains entry through the pharyngeal mucosa. After a 1- to 3-week incubation period, viral replication occurs in tonsillar and intestinal lymphoid tissues and associated lymph nodes. Up to 95% of all poliovirus infections are asymptomatic or so mild that they are clinically invisible. Viremia in 4% to 8% of infected individuals causes a mild illness with nonspecific symptoms including fever, sore throat, nausea, vomiting, and abdominal pain. One percent to 2% of polio infections cause nonparalytic aseptic meningitis. Less than 1% of polio infections result in paralysis.19
In paralytic poliomyelitis, viremia spreads infection to the CNS. Viral invasion and replication destroy motor neurons in the cortex, brainstem, and/or spinal cord.19 The risk and severity of paralytic poliomyelitis increases as the patient’s age increases. Ironically, although improvements in sanitation and a clean water supply reduce the transmission of poliovirus, these improvements also decrease opportunities for children to be infected in infancy, when mild, nonparalytic disease is more likely (Supplemental Digital Content, Ref. 45, http://links.lww.com/AA/B367). Disease severity can also be affected by other variables, including malnutrition, immune deficiency, and the location of CNS lesions.150
Paralytic poliomyelitis results from destruction of CNS neurons by the polio virus. The disease is further categorized into spinal, bulbar, and bulbospinal poliomyelitis. Paralytic poliomyelitis has a mortality rate of 5% to 10%.150 Spinal poliomyelitis is the most common form of paralytic poliomyelitis and causes flaccid paralysis in the limbs and atrophy of intercostal muscles. Sensation in the affected nerve distribution remains intact, and any limb or combination of limbs may be affected. Bulbar poliomyelitis comprises about 2% of the cases of paralytic polio and results in brainstem damage that affects control of breathing, speaking, and swallowing (Supplemental Digital Content, Refs. 46 and 47, http://links.lww.com/AA/B367).19 Approximately 20% of patients with paralytic polio display symptoms of both high spinal and bulbar nerve destruction, which is called bulbospinal poliomyelitis. Viral infection of the upper cervical spinal cord may cause diaphragmatic paralysis, dysphagia, paralysis of upper and lower extremities, and cardiac bradyarrhythmias. Patients with bulbospinal poliomyelitis are often rendered ventilator dependent. Both bulbar and bulbospinal poliomyelitis are associated with a significantly higher mortality rate (15%–75%) depending on access to positive pressure ventilation.19,151 In all types of paralytic polio, pain is a significant problem as sensory pathways remain intact.
Patients may develop new symptoms of weakness and fatigue decades after recovery from acute polio infection. This phenomenon is called postpolio syndrome (PPS) and is a noninfectious, progressive deterioration of motor neuron units, associated with age, recent acute illnesses, overuse, and disuse. Patients with PPS often experience chronic pain and cold intolerance.152,153 Like poliomyelitis, PPS is associated with specific anesthetic considerations discussed further in this section.
The anesthetic implications of acute nonparalytic poliovirus infection are few, and most patients recover fully. However, in cases of paralytic poliomyelitis, the implications are more significant. In the acute and subacute phase of paralytic polio, patients may experience more rapid and prolonged neuromuscular blockade with both depolarizing and nondepolarizing neuromuscular blocking drugs. In the chronic phase, the presence of oversized motor units may render patients susceptible to hyperkalemia with the use of succinylcholine, whereas the smaller total number of functional motor units increases sensitivity to nondepolarizing neuromuscular blockers.154 With these considerations in mind, any use of neuromuscular blockers should be undertaken with great caution and avoided altogether if possible. Few data inform the use of regional anesthesia in patients with paralytic polio infection. However, successful use of neuraxial anesthesia has been reported in patients with chronic disability because of polio or PPS.152,155,156 Despite the potential risk of nerve injury, regional anesthetic techniques are a reasonable alternative to general anesthesia in some patients because of the unpredictability of neuromuscular blockade and risk of exacerbating respiratory compromise.
Respiratory dysfunction is a common consequence of paralytic polio and may occur in the acute to subacute timeframe.157 Patients with dysphagia, cough after swallowing, dysphonia, dyspnea, tachypnea, prominent use of accessory muscles of respiration, or paradoxical breathing should be investigated thoroughly before a planned procedure with pulmonary function testing and analysis of arterial blood gases.157,158 Noninvasive positive pressure ventilation may be necessary during postoperative recovery, because symptoms of sleep-related disordered breathing may worsen after surgery.159 In addition, patients with bulbar and bulbospinal polio are at an increased risk of pulmonary aspiration. Up to 40% of PPS patients also experience respiratory symptoms caused by recurrent infections, scoliosis, reduced chest wall strength, and sleep-related disordered breathing.152 Dysphagia is present in 10% to 20% of patients with PPS and may increase the risk of aspiration.160
Cardiac arrhythmias may occur in patients who have had bulbar or bulbospinal polio. The type of arrhythmia varies depending on the location of the CNS lesions. Lesions in the high thoracic or low cervical spine may result in bradyarrhythmias attributable to disruption of cardiac accelerator fibers. Vagal nerve or vagal nucleus lesions may result in tachyarrhythmias attributable to unopposed sympathetic tone. Postpolio patients may also require medications or pacemakers to manage arrhythmias.152
In summary, the care of patients with paralytic poliomyelitis and PPS in the operating room and the intensive care unit is challenging because of respiratory, cardiovascular, and neuromuscular compromise. Although patients with polio and PPS are uncommon in US hospitals, HCP may encounter them while providing care in the developing world. Lessons learned from polio may also prove valuable when caring for patients affected by emerging infectious diseases such as a nonpolio enterovirus (D68), which was recently linked to a polio-like syndrome of acute flaccid paralysis in children in Colorado and California.161
TRANSMISSION PRECAUTIONS AND PERSONAL PROTECTIVE EQUIPMENT
All hospitalized patients require specialized procedures and equipment during their care to limit the spread of infectious diseases. A description of standard, contact, droplet, and airborne transmission precautions and the appropriate PPE for each as defined by the CDC is provided in Figure 3. Understanding the distinction between droplet and airborne transmission is crucial to appreciate the importance of specific transmission precautions and PPE for most VPDs. Respiratory pathogens are transmitted when small particles of infectious fluid generated by talking, coughing, and sneezing travel a short distance and contact the respiratory tract mucosal surfaces of a recipient. The larger the particle, the shorter the distance it travels and the more likely it is to deposit in the upper respiratory tract rather than lower respiratory tract. In WHO terminology, particles >5 μm in diameter are called “droplets,” generally travel <1 m from the source and tend to deposit in the upper airways. Standard fluid-resistant surgical masks prevent the majority of large droplets from being inhaled by HCP. Particles ≤5 μm in diameter are called “aerosols.” In contrast to droplets, aerosols can remain suspended in the air for long periods of time (hence, “airborne”) and are capable of being dispersed over large areas by air currents and ventilation systems. Aerosols are more likely to travel into the lower airways and to cause severe lower respiratory tract infections. Surgical masks do not seal tightly against the face and therefore do not prevent the inhalation of aerosols. HCP protection from aerosols instead requires the use of National Institute for Occupational Safety and Health-approved N95 respirators or powered air purifying respirators (Supplemental Digital Content, Refs. 25, 48, and 49, http://links.lww.com/AA/B367). Although the 5-μm limit conveniently separates droplet-transmitted from aerosol-transmitted pathogens, it is overly simplistic. In reality, coughing and sneezing generate a large number of particles that travel variable distances and range in size from <5 μm to >100 μm. Expelled droplets may also shrink because of evaporation, particularly in dry environments, and behave as aerosols.109,162 Although a few pathogens are known with certainty to be transmitted through aerosols, notably Mycobacterium tuberculosis smallpox, VZV, and measles viruses, there is a growing concern that severe acute respiratory syndrome-corona virus (SARS-CoV), influenza virus, and many other bacteria and viruses may exhibit airborne and droplet transmission (Supplemental Digital Content, Ref. 48, http://links.lww.com/AA/B367).109,162 The clinical implications of these dual modes of transmission with respect to modifying current precautionary guidelines are unclear.
The physical environment of care is particularly important in containing respiratory pathogens transmitted by aerosols. Manipulation of airflow within an airborne infection isolation room (AIIR) creates negative pressure in the room relative to adjacent areas, which limits the spread of contaminated air currents to the rest of the facility. Standards set by the American Institute of Architects/Facility Guidelines Institute and endorsed by the CDC stipulate that AIIRs have continuous negative pressure relative to the surrounding area, 12 air exchanges per hour (for new construction), and air that is exhausted directly to the outside or at recirculated through a High Efficiency Particulate Air filter (Supplemental Digital Content, Ref. 25, http://links.lww.com/AA/B367). Proper function of AIIRs must be monitored regularly.163,164 Although negative pressure helps to contain airborne particles, full PPE including respirators should be donned by HCP when entering these rooms. Airborne precautions for respiratory pathogens like measles virus and pandemic influenza virus, unlike the more familiar M tuberculosis, must also include gowns, gloves, and eye protection because transmission occurs through contact and droplets as well as aerosols (Fig. 3).
In the operating room, the major goal of PPE is to protect the patient from infection transmitted from the clinician, rather than the other way around. Prevention of nosocomial infection through hand hygiene, donning sterile gown and gloves, and limiting surgical site contamination from HCP respiratory droplets, sweat, and squamous cells by surgical masks and gowns are steps commonly taken. The protection of operating room staff from exposure to patient blood and other bodily fluids is a secondary, albeit very important goal, fulfilled by everyday PPE. When a patient suffers from a highly contagious and virulent respiratory tract infection, incorrect use of PPE can cause HCP deaths, as occurred during a large outbreak of SARS-CoV in Hong Kong.165 Furthermore, the infection of a nurse in Texas during the 2014 Ebola virus outbreak was linked to a possible breach of protocol in PPE removal, a procedure that is difficult to perform well without practice.166 In our experience, correct PPE donning and doffing procedures for droplet and airborne precautions are not routinely practiced by anesthesia providers during drills or simulation. Compliance with airborne precautions becomes particularly difficult in operating room environments, which are normally positive pressure environments relative to adjacent hallways to minimize the risk of air currents carrying pathogens into the room. In the case of a patient with measles, for example, aerosolized virus could travel from the operating room into the hallway every time the operating room door opens. For this reason, surgery should be avoided if at all possible on patients in airborne isolation for any reason. If an operation must occur in a patient with a severe airborne respiratory virus, tracheal intubation and extubation should occur in an AIIR, traffic into and out of the operating room should be minimized, and the room should be closed for at least 2 hours after the case so that at least 30 room air exchanges can occur (Supplemental Digital Content, Ref. 25, http://links.lww.com/AA/B367).163
Additionally concerning is the possible role of AGPs in the transmission of viruses normally spread only by droplets or mucosal surface contact with secretions. Aerosols are produced when air currents moving across the surface of a liquid film generate tiny particles at the air–liquid interface. The higher the velocity of air current, the smaller the particle. Any procedure that causes gas to travel at high velocity over respiratory tract mucosal surfaces can generate infectious aerosols. Medical procedures reported to generate aerosols include tracheal intubation and extubation, mask ventilation, open airway suctioning, bronchoscopy or upper airway endoscopy, noninvasive positive pressure ventilation, nasogastric feeding, nebulization, high-frequency oscillating ventilation, cardiopulmonary resuscitation, autopsy, and surgery (Supplemental Digital Content, Refs. 25 and 48, http://links.lww.com/AA/B367).167 Although the details are still unclear, there are many potential mechanisms that may cause aerosolization of bodily fluids during surgery, including the use of bone saws and drills, electrocautery, and high-pressure irrigation systems.168,169
Research on AGPs is extremely limited, and the few available studies are small and have methodologic flaws. The only systematic review of the 10 studies on AGPs and SARS-CoV transmission found that tracheal intubation, mask ventilation before intubation, and tracheotomy were the procedures most consistently linked to HCP infection.170 AGPs have been associated with transmission to HCP of other pathogens such as N meningitidis and Crimean-Congo hemorrhagic fever virus. The latter is particularly disturbing because this uncommon virus is normally transmitted through tick bites or through direct contact with infected bodily fluids and not through any known respiratory route (Supplemental Digital Content, Ref. 25, http://links.lww.com/AA/B367).171
Concerns about the possible role of AGPs in causing HCP infection during the Ebola virus outbreak in 2014 led both the CDC and WHO to upgrade their recommendations for transmission precautions to include airborne precautions, including the use of fluid-resistant particulate respirators, “during procedures that generate aerosols of body fluids” (Supplemental Digital Content, Refs. 50 and 51, http://links.lww.com/AA/B367). High-quality research is clearly needed in this area, because many questions remain unanswered. Clearly, however, the riskiest procedures are often performed by, or require the close involvement of, anesthesiologists and intensivists. In our opinion, airborne and contact precautions should be used in the care of patients undergoing AGPs with epidemiologically important viral respiratory tract infections normally transmitted by droplets. Attention to enhanced transmission precautions in the setting of uncommon VPDs or during pandemic acute respiratory illness would be necessary in the intensive care unit, operating room, emergency department, endoscopy suite, and any other areas where AGPs might be performed. By virtue of their presence in these areas, anesthesiologists are particularly well positioned to coordinate care and to ensure that appropriate transmission precautions are taken to prevent HCP infection and nosocomial outbreaks.
IMMUNIZATIONS FOR HEALTH CARE PERSONNEL
The CDC’s Advisory Committee on Immunization makes specific recommendations for HCP immunization and postexposure prophylaxis for a variety of pathogens summarized in Table 3. Additional vaccines may be recommended for HCP based on age or risk factors, including typhoid, pneumococcal, human papillomavirus, and hepatitis A vaccines. HCP working in other countries can be at an increased risk for infection with other VPDs such as hepatitis A, Japanese encephalitis, rabies, typhoid, and yellow fever. They should seek the advice of a health care provider familiar with travel medicine at least 4 to 6 weeks before travel to ensure that they are up-to-date on routine vaccinations and that they receive vaccinations appropriate for their destination.87 HCPs are not at a greater risk for pneumococcal disease than the general population. Pneumococcal vaccination for all adults older than 65 years, including HCP, is recommended. All adults with chronic heart or lung disease, functional or anatomic asplenia, immune compromise, and many other comorbidities should receive the pneumococcal vaccine, and single revaccination after 5 years is recommended for those with asplenia or immune compromise.172,173 HCP are also at no greater risk than the general population for invasive Hib disease. The Advisory Committee on Immunization Practices recommends 2 doses of Hib conjugate vaccine before 12 months of age, with no need for revaccination for otherwise healthy individuals. All adults with asplenia or immune compromise should receive the Hib vaccine.174
At our institution, new employees must document vaccinations for or immunity to MMR, diphtheria, tetanus, pertussis (Tdap), VZV, hepatitis B, and influenza. It is likely that these requirements are similar in other medical facilities nationwide. However, unlike robust school entry laws in all states that have demonstrated effectiveness in maintaining high vaccination rates among children, laws governing vaccination for HCP vary widely by state. Twelve states have no laws at all pertaining to vaccination status in HCP. Twenty-one others have “offer” laws, meaning that a particular vaccination should be offered but is optional at the discretion of the employee. Only 15 states have “ensure” laws, meaning that vaccination is mandatory in the absence of a specific exemption or refusal. The laws are highly variable in the type of vaccination required, and states may have both “offer” and “ensure” laws for different vaccines. Some laws focus on hepatitis B alone, others emphasize the MMR vaccine, and only a few address VZV or influenza. Some laws are applicable to only certain groups of HCP, such as those in contact with pediatric patients or women of childbearing age, or are applicable only in specific types of health care facilities. Despite CDC recommendations that all hospital employees receive the MMR vaccine, only 10 states require this precaution by law. Of these, 7 states allow exemptions for medical, philosophical, or religious reasons. Only 3 states require influenza vaccinations for HCP even though influenza is a leading cause of death among adults in the United States and costs the health care system 3 to 5 billion dollars annually (Supplemental Digital Content, Ref. 52, http://links.lww.com/AA/B367).175–177
Since 1981, the CDC has recommended influenza vaccination for all HCP. However, HCP flu vaccination coverage has hovered between 65% and 75% since 2011, well below the national goal of 90% (Supplemental Digital Content, Ref. 53, http://links.lww.com/AA/B367).178 HCP compliance with influenza vaccination is relatively poor for several reasons, including belief that influenza is a mild illness, belief that the vaccine is not effective, fear of adverse effects, and belief that they are not at risk of contracting or transmitting influenza.179 Unfortunately, unvaccinated HCP can be the source of outbreaks of influenza in the health care setting, and evidence suggests that they can be the predominant source.180–183 Nosocomial outbreaks of influenza are associated with a median patient mortality rate of 16% and up to 60% in critically ill and immunocompromised patients.181 HCP flu vaccination is cost-effective and indirectly reduces infection in high-risk patients, although the latter has not been conclusively demonstrated in adults older than 60 years in long-term care facilities.181,184 HCP appear to be at higher risk of contracting influenza when compared with adults working in non-health care settings.185 Simply avoiding patient contact when ill is an ineffective strategy, because individuals can shed virus before the development of symptoms.178 Furthermore, “presenteeism,” or working while ill, is common in HCP and places both patients and coworkers at risk.182 The collective evidence regarding HCP influenza vaccination demonstrates a reduction in the risk of nosocomial influenza, reduction in patient morbidity and all-cause mortality, reduction in health care utilization costs and disruption of care during influenza season, and reduced symptoms of upper respiratory illness and need for sick days in HCP.182,186
For these reasons, increasing influenza vaccination rates in HCP has been a major public health goal for years. Vaccination rates improve during focused campaigns that include education, publicity, and employee incentives, yet rarely exceed 70% and are difficult to sustain.187 Mandatory influenza vaccination programs, that is, linking flu vaccination to continued employment, are controversial but have resulted in sustained HCP vaccination rates over 90% at some medical centers.178 Furthermore, this strategy has also been highly effective to ensure hepatitis B, rubella, and Tdap vaccination in HCP.177,188 Annual vaccination against influenza as a condition of employment is recommended by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology, the American College of Physicians, the National Patient Safety Foundation, and many other medical organizations.188 In addition, the National Quality Forum lists influenza immunization of HCP as 1 of 34 practices that should be used universally to reduce the risk of patient harm (Supplemental Digital Content, Ref. 54, http://links.lww.com/AA/B367). The Joint Commission on Accreditation of Healthcare Organizations now expects that health care organizations set incremental HCP influenza vaccination goals to meet the 90% rate established by national initiatives by 2020 (Supplemental Digital Content, Ref. 55, http://links.lww.com/AA/B367).
VPDs are becoming more prevalent in the United States. Underimmunized populations, waning immunity after past vaccination, pathogen genetic adaptation, and an unprecedented ease of travel by individuals to and from areas where VPDs are endemic are all contributory factors. In addition, public misconceptions about the danger and efficacy of vaccinations are having adverse effects on herd immunity in the United States. Hospital-based physicians such as anesthesiologists and intensivists should be prepared to diagnose and treat patients with VPDs, while protecting themselves, their own families, and other patients from infection. Vigilance is particularly important for clinicians who perform AGPs, whose health may be jeopardized while caring for patients with high-risk viral infections.
Steps can be taken immediately to improve patient and HCP safety. First and foremost, clinicians should educate themselves about the importance and limitations of vaccines and the severe manifestations of VPDs likely to be seen in hospitalized patients. Second, they should check their own immunization status and stay up-to-date on recommended immunizations. Third, they should educate patients and colleagues about the importance and limitations of vaccination. Fourth, they should ask about the policies in place at their own institutions regarding transmission precautions and employee immunization. Finally, they should become leaders in periprocedural areas about transmission precautions and PPE, particularly in regard to AGPs. The increasing incidence of VPDs in the United States and Europe and the persistence of VPDs globally means that all clinicians must be prepared to manage infectious diseases previously believed to be controlled or eliminated to deliver the highest quality of care to all patients.
Name: Grete H. Porteous, MD.
Contribution: This author assisted with the article concept, background research, manuscript preparation, and figure and table preparation.
Attestation: Grete H. Porteous approved the final manuscript and is the archival author.
Name: Neil A. Hanson, MD.
Contribution: This author assisted with the article concept, background research, manuscript preparation, and figure and table preparation.
Attestation: Neil A. Hanson approved the final manuscript.
Name: Lila Ann A. Sueda, MD.
Contribution: This author assisted with the background research and manuscript preparation.
Attestation: Lila Ann A. Sueda approved the final manuscript.
Name: Carli D. Hoaglan, MD.
Contribution: This author assisted with the background research and manuscript preparation.
Attestation: Carli D. Hoaglan approved the final manuscript.
Name: Aaron B. Dahl, MD.
Contribution: This author assisted with the background research and manuscript preparation.
Attestation: Aaron B. Dahl approved the final manuscript.
Name: Brooks B. Ohlson, MD
Contribution: This author assisted with the background research and manuscript preparation.
Attestation: Brooks B. Ohlson approved the final manuscript.
Name: Brian E. Schmidt, MD.
Contribution: This author assisted with the background research and manuscript preparation.
Attestation: Brian E. Schmidt approved the final manuscript.
Name: Chia C. Wang, MD.
Contribution: This author assisted with the background research and manuscript preparation.
Attestation: Chia C. Wang approved the final manuscript.
Name: R. Eliot Fagley, MD.
Contribution: This author assisted with the article concept, background research, manuscript preparation, and figure and table preparation.
Attestation: R. Eliot Fagley approved the final manuscript.
This manuscript was handled by: Avery Tung, MD.
1. Moturi EK, Porter KA, Wassilak SG, Tangermann RH, Diop OM, Burns CC, Jafari H. Progress toward polio eradication—worldwide, 2013-2014. MMWR Morb Mortal Wkly Rep. 2014;63:468–72
2. Stern AM, Markel H. The history of vaccines and immunization: familiar patterns, new challenges. Health Aff (Millwood). 2005;24:611–21
3. Centers for Disease Control and Prevention. . Vaccine preventable deaths and the global immunization vision and strategy, 2006–2015. MMWR Morb Mortal Wkly Rep. 2006;55:511–5
4. Omer SB, Salmon DA, Orenstein WA, deHart MP, Halsey N. Vaccine refusal, mandatory immunization, and the risks of vaccine-preventable diseases. N Engl J Med. 2009;360:1981–8
5. Dubé E, Vivion M, MacDonald NE. Vaccine hesitancy, vaccine refusal and the anti-vaccine movement: influence, impact and implications. Expert Rev Vaccines. 2015;14:99–117
6. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet. 1998;351:637–41
7. Jain A, Marshall J, Buikema A, Bancroft T, Kelly JP, Newschaffer CJ. Autism occurrence by MMR vaccine status among US children with older siblings with and without autism. JAMA. 2015;313:1534–40
8. Demicheli V, Rivetti A, Debalini MG, Di Pietrantonj C. Vaccines for measles, mumps and rubella in children. Cochrane Database Syst Rev. 2012;2:CD004407
9. Rao TS, Andrade C. The MMR vaccine and autism: sensation, refutation, retraction, and fraud. Indian J Psychiatry. 2011;53:95–6
10. Gerber JS, Offit PA. Vaccines and autism: a tale of shifting hypotheses. Clin Infect Dis. 2009;48:456–61
11. Siddiqui M, Salmon DA, Omer SB. Epidemiology of vaccine hesitancy in the United States. Hum Vaccin Immunother. 2013;9:2643–8
13. Adams DA, Jajosky RA, Ajani U, Kriseman J, Sharp P, Onwen DH, Schley AW, Anderson WJ, Grigoryan A, Aranas AE, Wodajo MS, Abellera JPCenters for Disease Control and Prevention (CDC). . Summary of notifiable diseases—United States, 2012. MMWR Morb Mortal Wkly Rep. 2014;61:1–121
14. Zipprich J, Winter K, Hacker J, Xia D, Watt J, Harriman KCenters for Disease Control and Prevention (CDC). . Measles outbreak—California, December 2014-February 2015. MMWR Morb Mortal Wkly Rep. 2015;64:153–4
15. Berzofsky JA, Ahlers JD, Belyakov IM. Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol. 2001;1:209–19
16. Hamborsky J, Kroger A, Wolfe CCenters for Disease Control and Prevention. . Principles of vaccination. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. 201513th ed. Washington, D.C. Public Health Foundation
17. Zhang N, Zheng BJ, Lu L, Zhou Y, Jiang S, Du L. Advancements in the development of subunit influenza vaccines. Microbes Infect. 2015;17:123–34
18. Leuridan E, Van Damme P. Passive transmission and persistence of naturally acquired or vaccine-induced maternal antibodies against measles in newborns. Vaccine. 2007;25:6296–304
19. Hamborsky J, Kroger A, Wolfe CCenters for Disease Control and Prevention. . Chapter by pathogen. In: Epidemiology and Prevention of Vaccine-Preventable Disease. 201513 ed. Washington, D.C. Public Health Foundation Available at: http://www.cdc.gov/vaccines/pubs/pinkbook/index.html
. Accessed Deceber 12, 2015
20. Centers for Disease Control and Prevention (CDC). . Measles pneumonitis following measles-mumps-rubella vaccination of a patient with HIV infection, 1993. MMWR Morb Mortal Wkly Rep. 1996;45:603–6
21. Elllis D, Gilboa N, Bellinger M, Shapiro RShapiro R, Simmons SR, Starzl TE. Renal transplantation in adults and children. In: Renal Transplantation. 1997;461 Stamford, CT Appleton and Lange
22. Bridges CB, Coyne-Beasley TAdvisory Committee on Immunization Practices. . Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older: United States, 2014. Ann Intern Med. 2014;160:190
23. Akinsanya-Beysolow IAdvisory Committee on Immunization Practices (ACIP); ACIP Child/Adolescent Immunization Work Group; Centers for Disease Control and Prevention (CDC). . Advisory Committee on Immunization Practices recommended immunization schedules for persons aged 0 through 18 years—United States, 2014. MMWR Morb Mortal Wkly Rep. 2014;63:108–9
24. Topley WW, Wilson GS. The spread of bacterial infection. The problem of herd-immunity. J Hyg (Lond). 1923;21:243–9
25. Fine P, Eames K, Heymann DL. “Herd immunity”: a rough guide. Clin Infect Dis. 2011;52:911–6
26. Stephens DS. Vaccines for the unvaccinated: protecting the herd. J Infect Dis. 2008;197:643–5
27. Fine PE. Herd immunity: history, theory, practice. Epidemiol Rev. 1993;15:265–302
28. Cherry JD. Why do pertussis vaccines fail? Pediatrics. 2012;129:968–70
29. Plans-Rubió P. The vaccination coverage required to establish herd immunity against influenza viruses. Prev Med. 2012;55:72–7
30. Ramsay ME, Moffatt D, O’Connor M. Measles vaccine: a 27-year follow-up. Epidemiol Infect. 1994;112:409–12
31. Siebert JN, Posfay-Barbe KM, Habre W, Siegrist CA. Influence of anesthesia on immune responses and its effect on vaccination in children: review of evidence. Paediatr Anaesth. 2007;17:410–20
32. Nafiu OO, Lewis I. Vaccination and anesthesia: more questions than answers. Paediatr Anaesth. 2007;17:1215
33. Nichol KL, Lind A, Margolis KL, Murdoch M, McFadden R, Hauge M, Magnan S, Drake M. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med. 1995;333:889–93
34. Haber P, DeStefano F, Angulo FJ, Iskander J, Shadomy SV, Weintraub E, Chen RT. Guillain-Barré syndrome following influenza vaccination. JAMA. 2004;292:2478–81
35. Haber P, Sejvar J, Mikaeloff Y, DeStefano F. Vaccines and Guillain-Barré syndrome. Drug Saf. 2009;32:309–23
36. Yih WK, Weintraub E, Kulldorff M. No risk of Guillain-Barré syndrome found after meningococcal conjugate vaccination in two large cohort studies. Pharmacoepidemiol Drug Saf. 2012;21:1359–60
37. Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE. Individual and community risks of measles and pertussis associated with personal exemptions to immunization. JAMA. 2000;284:3145–50
38. Omer SB, Richards JL, Ward M, Bednarczyk RA. Vaccination policies and rates of exemption from immunization, 2005-2011. N Engl J Med. 2012;367:1170–1
39. Centers for Disease Control and Prevention. . Vaccination coverage among children in kindergarten—United States, 2012–13 school year. MMWR Morb Mortal Wkly Rep. 2013;62:607–12
40. Centers for Disease Control and Prevention. . Measles—United States, January 4-April 2, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:373–6
41. Muscat M. Who gets measles in Europe? J Infect Dis. 2011;204(suppl 1):S353–65
42. Gushulak BD, MacPherson DW. Globalization of infectious diseases: the impact of migration. Clin Infect Dis. 2004;38:1742–8
44. Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis. 2004;189(suppl 1):S4–16
45. Bazan JA, Mangino JE. Infection control and postexposure prophylaxis for the pregnant healthcare worker. Clin Obstet Gynecol. 2012;55:571–88
46. Parker AA, Staggs W, Dayan GH, Ortega-Sánchez IR, Rota PA, Lowe L, Boardman P, Teclaw R, Graves C, LeBaron CW. Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. N Engl J Med. 2006;355:447–55
47. Dallaire F, De Serres G, Tremblay FW, Markowski F, Tipples G. Long-lasting measles outbreak affecting several unrelated networks of unvaccinated persons. J Infect Dis. 2009;200:1602–5
48. Gahr P, DeVries AS, Wallace G, Miller C, Kenyon C, Sweet K, Martin K, White K, Bagstad E, Hooker C, Krawczynski G, Boxrud D, Liu G, Stinchfield P, LeBlanc J, Hickman C, Bahta L, Barskey A, Lynfield R. An outbreak of measles in an undervaccinated community. Pediatrics. 2014;134:e220–8
49. Mina MJ, Metcalf CJ, de Swart RL, Osterhaus AD, Grenfell BT. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science. 2015;348:694–9
50. Kaplan LJ, Daum RS, Smaron M, McCarthy CA. Severe measles in immunocompromised patients. JAMA. 1992;267:1237–41
51. Gremillion DH, Crawford GE. Measles pneumonia in young adults. An analysis of 106 cases. Am J Med. 1981;71:539–42
52. Rafat C, Klouche K, Ricard JD, Messika J, Roch A, Machado S, Sonneville R, Guisset O, Pujol W, Guerin C, Teboul JL, Mrozek N, Darmon M, Chemouni F, Schmidt M, Mercier E, Dreyfuss D, Gaudry S. Severe measles infection: the spectrum of disease in 36 critically ill adult patients. Medicine. 2013;92:257–72
53. Fisher DL, Defres S, Solomon T. Measles-induced encephalitis. QJM. 2015;108:177–82
54. Centers for Disease Control and Prevention. . Measles prevention: recommendations of the immunization practices advisory committee (ACIP). MMWR Morb Mortal Wkly Rep. 1989;38(S-9):1–18
55. Fiebelkorn AP, Seward JF, Orenstein WA. A global perspective of vaccination of healthcare personnel against measles: systematic review. Vaccine. 2014;32:4823–39
56. Dayan GH, Quinlisk MP, Parker AA, Barskey AE, Harris ML, Schwartz JM, Hunt K, Finley CG, Leschinsky DP, O’Keefe AL, Clayton J, Kightlinger LK, Dietle EG, Berg J, Kenyon CL, Goldstein ST, Stokley SK, Redd SB, Rota PA, Rota J, Bi D, Roush SW, Bridges CB, Santibanez TA, Parashar U, Bellini WJ, Seward JF. Recent resurgence of mumps in the United States. N Engl J Med. 2008;358:1580–9
57. Cohen C, White JM, Savage EJ, Glynn JR, Choi Y, Andrews N, Brown D, Ramsay ME. Vaccine effectiveness estimates, 2004-2005 mumps outbreak, England. Emerg Infect Dis. 2007;13:12–7
58. Harling R, White JM, Ramsay ME, Macsween KF, van den Bosch C. The effectiveness of the mumps component of the MMR vaccine: a case control study. Vaccine. 2005;23:4070–4
59. Cortese MM, Jordan HT, Curns AT, Quinlan PA, Ens KA, Denning PM, Dayan GH. Mumps vaccine performance among university students during a mumps outbreak. Clin Infect Dis. 2008;46:1172–80
60. Date AA, Kyaw MH, Rue AM, Klahn J, Obrecht L, Krohn T, Rowland J, Rubin S, Safranek TJ, Bellini WJ, Dayan GH. Long-term persistence of mumps antibody after receipt of 2 measles-mumps-rubella (MMR) vaccinations and antibody response after a third MMR vaccination among a university population. J Infect Dis. 2008;197:1662–8
61. Galazka AM, Robertson SE, Kraigher A. Mumps and mumps vaccine: a global review. Bull World Health Organ. 1999;77:3–14
62. Beard CM, Benson RC Jr, Kelalis PP, Elveback LR, Kurland LT. The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc. 1977;52:3–7
63. Russell RR, Donald JC. The neurological complications of mumps. Br Med J. 1958;2:27–30
64. Siegel M, Fuerst HT, Peress NS. Comparative fetal mortality in maternal virus diseases. A prospective study on rubella, measles, mumps, chicken pox and hepatitis. N Engl J Med. 1966;274:768–71
65. Lambert N, Strebel P, Orenstein W, Icenogle J, Poland GA. Rubella. Lancet. 2015;385:2297–307
66. Simic D, Milojevic I. Acute myocarditis during anesthesia after rubella infection. Paediatr Anaesth. 2008;18:1135–6
67. Cutts FT, Robertson SE, Diaz-Ortega JL, Samuel R. Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: burden of disease from CRS. Bull World Health Organ. 1997;75:55–68
68. Reef S. RubellaHeymann DL In: Control of Communicable Diseases Manual. 201420th ed Washington, D.C. American Public Health Association
69. Robertson SE, Featherstone DA, Gacic-Dobo M, Hersh BS. Rubella and congenital rubella syndrome: global update. Rev Panam Salud Publica. 2003;14:306–15
71. Centers for Disease Control and Prevention. . Three cases of congenital rubella syndrome in the postelimination era—Maryland, Alabama, and Illinois, 2012. MMWR Morb Mortal Wkly Rep. 2013;62:226–9
72. Hariharan U, Garg R, Nagpal VK, Pawar M. Combined cardiac and noncardiac surgery in an infant with congenital rubella syndrome: an anesthetic challenge. Paediatr Anaesth. 2011;21:1168–9
73. Souki F, Shettar SS. Prolonged respiratory depression after general anesthesia in an adult with congenital rubella syndrome. A A Case Rep. 2013;1:46–8
74. Winter K, Glaser C, Watt J, Harriman KCenters for Disease Control and Prevention (CDC). . Pertussis epidemic—California, 2014. MMWR Morb Mortal Wkly Rep. 2014;63:1129–32
75. Brooks DA, Clover R. Pertussis infection in the United States: role for vaccination of adolescents and adults. J Am Board Fam Med. 2006;19:603–11
76. Hartzell JD, Blaylock JM. Whooping cough in 2014 and beyond: an update and review. Chest. 2014;146:205–14
77. Rothstein E, Edwards K. Health burden of pertussis in adolescents and adults. Pediatr Infect Dis J. 2005;24:S44–7
78. Kretsinger K, Broder KR, Cortese MM, Joyce MP, Ortega-Sanchez I, Lee GM, Tiwari T, Cohn AC, Slade BA, Iskander JK, Mijalski CM, Brown KH, Murphy TVCenters for Disease Control and Prevention; Advisory Committee on Immunization Practices; Healthcare Infection Control Practices Advisory Committee. . Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR Recomm Rep. 2006;55:1–37
79. McGirr A, Fisman DN. Duration of pertussis immunity after DTaP immunization: a meta-analysis. Pediatrics. 2015;135:331–43
80. Mooi FR, van Loo IH, van Gent M, He Q, Bart MJ, Heuvelman KJ, de Greeff SC, Diavatopoulos D, Teunis P, Nagelkerke N, Mertsola J. Bordetella pertussis strains with increased toxin production associated with pertussis resurgence. Emerg Infect Dis. 2009;15:1206–13
81. Mooi FR, Van Der Maas NA, De Melker HE. Pertussis resurgence: waning immunity and pathogen adaptation—two sides of the same coin. Epidemiol Infect. 2014;142:685–94
82. Cherry JD. The epidemiology of pertussis: a comparison of the epidemiology of the disease pertussis with the epidemiology of Bordetella pertussis infection. Pediatrics. 2005;115:1422–7
83. Sandora TJ, Gidengil CA, Lee GM. Pertussis vaccination for health care workers. Clin Microbiol Rev. 2008;21:426–34
84. Bisgard KM, Pascual FB, Ehresmann KR, Miller CA, Cianfrini C, Jennings CE, Rebmann CA, Gabel J, Schauer SL, Lett SM. Infant pertussis: who was the source? Pediatr Infect Dis J. 2004;23:985–9
85. Lu PJ, Graitcer SB, O’Halloran A, Liang JL. Tetanus, diphtheria and acellular pertussis (Tdap) vaccination among healthcare personnel-United States, 2011. Vaccine. 2014;32:572–8
86. Williams WW, Lu PJ, O’Halloran A, Bridges CB, Kim DK, Pilishvili T, Hales CM, Markowitz LECenters for Disease Control and Prevention (CDC). . Vaccination coverage among adults, excluding influenza vaccination—United States, 2013. MMWR Morb Mortal Wkly Rep. 2015;64:95–102
87. Centers for Disease Control and Prevention. . Immunization of health-care personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60:1–45
88. McLean HQ, Fiebelkorn AP, Temte JL, Wallace GSCenters for Disease Control and Prevention. . Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62:1–34
89. Bisgard KM, Rhodes P, Hardy IR, Litkina IL, Filatov NN, Monisov AA, Wharton M. Diphtheria toxoid vaccine effectiveness: a case-control study in Russia. J Infect Dis. 2000;181(supp`l 1):S184–7
90. Vitek CR, Wharton M. Diphtheria in the former Soviet Union: reemergence of a pandemic disease. Emerg Infect Dis. 1998;4:539–50
91. Wagner KS, White JM, Crowcroft NS, De Martin S, Mann G, Efstratiou A. Diphtheria in the United Kingdom, 1986-2008: the increasing role of Corynebacterium ulcerans. Epidemiol Infect. 2010;138:1519–30
92. Hadfield TL, McEvoy P, Polotsky Y, Tzinserling VA, Yakovlev AA. The pathology of diphtheria. J Infect Dis. 2000;181(suppl 1):S116–20
93. Jennis F, Bale PM. Fatal respiratory and gastric diphtheria in an adult. Med J Aust. 1966;2:760–2
94. Farizo KM, Strebel PM, Chen RT, Kimbler A, Cleary TJ, Cochi SL. Fatal respiratory disease due to Corynebacterium diphtheriae
: case report and review of guidelines for management, investigation, and control. Clin Infect Dis. 1993;16:59–68
95. Washington CH, Issaranggoon na ayuthaya S, Makonkawkeyoon K, Oberdorfer P. A 9-year-old boy with severe diphtherial infection and cardiac complications. BMJ Case Rep. 2014;pii:bcr2014206085
96. Khodaei I, Sinha A, Dingle A. Diphtheria: a case report. J Laryngol Otol. 2008;122:1397–400
97. Lee JK, Huda S, Francis A, Aisai, Jusoh M. Respiratory diphtheria in three paediatric patients. Med J Malaysia. 1999;54:377–82
98. Sasidaran K, Bansal A, Singhi S. Acute upper airway obstruction. Indian J Pediatr. 2011;78:1256–61
99. Ganeshalingham A, Murdoch I, Davies B, Menson E. Fatal laryngeal diphtheria in a UK child. Arch Dis Child. 2012;97:748–9
100. Claus H, Maiden MC, Wilson DJ, McCarthy ND, Jolley KA, Urwin R, Hessler F, Frosch M, Vogel U. Genetic analysis of meningococci carried by children and young adults. J Infect Dis. 2005;191:1263–71
101. Cohn AC, MacNeil JR, Clark TA, Ortega-Sanchez IR, Briere EZ, Meissner HC, Baker CJ, Messonnier NECenters for Disease Control and Prevention (CDC). . Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62:1–28
102. Cohn AC, MacNeil JR, Harrison LH, Hatcher C, Theodore J, Schmidt M, Pondo T, Arnold KE, Baumbach J, Bennett N, Craig AS, Farley M, Gershman K, Petit S, Lynfield R, Reingold A, Schaffner W, Shutt KA, Zell ER, Mayer LW, Clark T, Stephens D, Messonnier NE. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease. Clin Infect Dis. 2010;50:184–91
103. Kirsch EA, Barton RP, Kitchen L, Giroir BP. Pathophysiology, treatment and outcome of meningococcemia: a review and recent experience. Pediatr Infect Dis J. 1996;15:967–78
104. Kortepeter MG, Adams BL, Zollinger WD, Gasser RA Jr. Fulminant supraglottitis from Neisseria meningitidis. Emerg Infect Dis. 2007;13:502–4
105. Maiden MC, Ibarz-Pavón AB, Urwin R, Gray SJ, Andrews NJ, Clarke SC, Walker AM, Evans MR, Kroll JS, Neal KR, Ala’aldeen DA, Crook DW, Cann K, Harrison S, Cunningham R, Baxter D, Kaczmarski E, Maclennan J, Cameron JC, Stuart JM. Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity. J Infect Dis. 2008;197:737–43
106. van Deuren M, Brandtzaeg P, van der Meer JW. Update on meningococcal disease with emphasis on pathogenesis and clinical management. Clin Microbiol Rev. 2000;13:144–66
107. Taubenberger JK, Morens DM. 1918 Influenza: the mother of all pandemics. Emerg Infect Dis. 2006;12:15–22
108. Webster RG, Walker EG. Influenza. Am Sci. 2003;91:122–9
109. Tellier R. Review of aerosol transmission of influenza A virus. Emerg Infect Dis. 2006;12:1657–62
110. Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med. 2008;121:258–64
111. Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis. 2009;9:493–504
112. Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011;377:1264–75
113. Girard MP, Tam JS, Assossou OM, Kieny MP. The 2009 A (H1N1) influenza virus pandemic: a review. Vaccine. 2010;28:4895–902
114. Horimoto T, Kawaoka Y. Influenza: lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol. 2005;3:591–600
115. Van Kerkhove MD, Hirve S, Koukounari A, Mounts AWH1N1pdm Serology Working Group. . Estimating age-specific cumulative incidence for the 2009 influenza pandemic: a meta-analysis of A(H1N1)pdm09 serological studies from 19 countries. Influenza Other Respir Viruses. 2013;7:872–86
116. Shrestha SS, Swerdlow DL, Borse RH, Prabhu VS, Finelli L, Atkins CY, Owusu-Edusei K, Bell B, Mead PS, Biggerstaff M, Brammer L, Davidson H, Jernigan D, Jhung MA, Kamimoto LA, Merlin TL, Nowell M, Redd SC, Reed C, Schuchat A, Meltzer MI. Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010). Clin Infect Dis. 2011;52(suppl 1):S75–82
117. Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, Vugia D, Harriman K, Matyas B, Glaser CA, Samuel MC, Rosenberg J, Talarico J, Hatch DCalifornia Pandemic (H1N1) Working Group. . Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA. 2009;302:1896–902
118. Cui W, Zhao H, Lu X, Wen Y, Zhou Y, Deng B, Wang Y, Wang W, Kang J, Liu P. Factors associated with death in hospitalized pneumonia patients with 2009 H1N1 influenza in Shenyang, China. BMC Infect Dis. 2010;10:145
119. Campbell A, Rodin R, Kropp R, Mao Y, Hong Z, Vachon J, Spika J, Pelletier L. Risk of severe outcomes among patients admitted to hospital with pandemic (H1N1) influenza. CMAJ. 2010;182:349–55
120. Roch A, Lepaul-Ercole R, Grisoli D, Bessereau J, Brissy O, Castanier M, Dizier S, Forel JM, Guervilly C, Gariboldi V, Collart F, Michelet P, Perrin G, Charrel R, Papazian L. Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study. Intensive Care Med. 2010;36:1899–905
121. Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza. Crit Care Med. 2010;38:e91–7
122. Reed C, Kim IK, Singleton JA, Chaves SS, Flannery B, Finelli L, Fry A, Burns E, Gargiullo P, Jernigan D, Cox N, Bresee JCenters for Disease Control and Prevention (CDC). . Estimated influenza illnesses and hospitalizations averted by vaccination—United States, 2013-14 influenza season. MMWR Morb Mortal Wkly Rep. 2014;63:1151–4
123. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:36–44
124. Puig-Barbera J, Mira-Iglesias A, Tortajada-Girbes M, Lopez-Labrador FX, Belenguer-Varea A, Carballido-Fernandez M, Carbonell-Franco E, Carratala-Munuera C, Limon-Ramirez R, Mollar-Maseres J, Del Carmen Otero-Reigada M, Schwarz-Chavarri G, Tuells J, Gil-Guillen VValencia Hospital Network for the Study of Influenza and Respiratory Viruses Disease. . Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results. Euro Surveill. 2015;20:21044
125. Shinjoh M, Sugaya N, Yamaguchi Y, Tomidokoro Y, Sekiguchi S, Mitamura K, Fujino M, Shiro H, Komiyama O, Taguchi N, Nakata Y, Yoshida N, Narabayashi A, Myokai M, Sato M, Furuichi M, Baba H, Fujita H, Sato A, Ookawara I, Tsunematsu K, Yoshida M, Kono M, Tanaka F, Kawakami C, Kimiya T, Takahashi T, Iwata SKeio Pediatric Influenza Research Group. . Effectiveness of trivalent inactivated influenza vaccine in children estimated by a test-negative case-control design study based on influenza rapid diagnostic test results. PLoS One. 2015;10:e0136539
126. Sambhara S, McElhaney JE. Immunosenescence and influenza vaccine efficacy. Curr Top Microbiol Immunol. 2009;333:413–29
127. Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. 2006;24:1159–69
128. Jefferson T, Rivetti D, Rivetti A, Rudin M, Di Pietrantonj C, Demicheli V. Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet. 2005;366:1165–74
129. Reichert TA, Sugaya N, Fedson DS, Glezen WP, Simonsen L, Tashiro M. The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med. 2001;344:889–96
130. Saxén H, Virtanen M. Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers. Pediatr Infect Dis J. 1999;18:779–83
131. Sengupta N, Breuer J. A global perspective of the epidemiology and burden of varicella-zoster virus. Curr Pediatr Rev. 2009;5:207–28
132. American Academy of Pediatrics Committee on Infectious Diseases. . Varicella vaccine update. Pediatrics. 2000;105:136–41
133. Mohsen AH, McKendrick M. Varicella pneumonia in adults. Eur Respir J. 2003;21:886–91
134. Marin M, Watson TL, Chaves SS, Civen R, Watson BM, Zhang JX, Perella D, Mascola L, Seward JF. Varicella among adults: data from an active surveillance project, 1995–2005. J Infect Dis. 2008;197(suppl 2):S94–100
135. Weber DM, Pellecchia JA. Varicella pneumonia: study of prevalence in adult men. JAMA. 1965;192:572–3
136. Zhang HJ, Patenaude V, Abenhaim HA. Maternal outcomes in pregnancies affected by varicella zoster virus infections: population-based study on 7.7 million pregnancy admissions. J Obstet Gynaecol Res. 2015;41:62–8
137. Feldman S. Varicella-zoster virus pneumonitis. Chest. 1994;106:22S–7S
138. Gnann JW Jr. Varicella-zoster virus: atypical presentations and unusual complications. J Infect Dis. 2002;186(suppl 1):S91–8
139. Zamula E. A new challenge for former polio patients. FDA Consumer. 1991;25:21
140. Pincock S. Bjørn Aage Ibsen. Lancet. 2007;370:1538
141. Porter KA, Diop OM, Burns CC, Tangermann RH, Wassilak SG. Tracking progress toward polio eradication—worldwide, 2013-2014. MMWR Morb Mortal Wkly Rep. 2015;64:415–20
145. Luo HM, Zhang Y, Wang XQ, Yu WZ, Wen N, Yan DM, Wang HQ, Wushouer F, Wang HB, Xu AQ, Zheng JS, Li DX, Cui H, Wang JP, Zhu SL, Feng ZJ, Cui FQ, Ning J, Hao LX, Fan CX, Ning GJ, Yu HJ, Wang SW, Liu DW, Wang DY, Fu JP, Gou AL, Zhang GM, Huang GH, Chen YS, Mi SS, Liu YM, Yin DP, Zhu H, Fan XC, Li XL, Ji YX, Li KL, Tang HS, Xu WB, Wang Y, Yang WZ. Identification and control of a poliomyelitis outbreak in Xinjiang, China. N Engl J Med. 2013;369:1981–90
147. Ahmad N, Drew WL, Lagunoff MRyan KJ, Ray CG. Enteroviruses. In: Sherris Medical Microbiology. 20146th ed New York, NY McGraw Hill
148. . Poliomyelitis prevention: recommendations for use of inactivated poliovirus vaccine and live oral poliovirus vaccine. American Academy of Pediatrics Committee on Infectious Diseases. Pediatrics. 1997;99:300–5
149. Kew OM, Sutter RW, de Gourville EM, Dowdle WR, Pallansch MA. Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol. 2005;59:587–635
150. Mueller S, Wimmer E, Cello J. Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. Virus Res. 2005;111:175–93
151. Hoyt W, Miller N, Walsh F Walsh and Hoyt’s Clinical Neuro-ophthalmology. 2005 Hagerstown, MD Lippincott Williams & Wilkins
152. Lambert DA, Giannouli E, Schmidt BJ. Postpolio syndrome and anesthesia. Anesthesiology. 2005;103:638–44
153. Jubelt B. Post-polio syndrome. Curr Treat Options Neurol. 2004;6:87–93
154. Daube JR, Windebank AJ, Litchy WJ. Electrophysiologic changes in neuromuscular function over five years in polio survivors. Ann N Y Acad Sci. 1995;753:120–8
155. Kumari BG, Samantaray A, Kumar VA, Durga P, Jagadesh G. Spinal anaesthesia in poliomyelitis patients with scoliotic spine: a case control study. Indian J Anaesth. 2013;57:145–9
156. Hebl JR, Horlocker TT, Schroeder DR. Neuraxial anesthesia and analgesia in patients with preexisting central nervous system disorders. Anesth Analg. 2006;103:223–8
157. Rezania K, Goldenberg FD, White S. Neuromuscular disorders and acute respiratory failure: diagnosis and management. Neurol Clin. 2012;30:161–85, viii
158. Soliman MG, Higgins SE, El-Kabir DR, Davidson AC, Williams AJ, Howard RS. Non-invasive assessment of respiratory muscle strength in patients with previous poliomyelitis. Respir Med. 2005;99:1217–22
159. Gillis-Haegerstrand C, Markström A, Barle H. Bi-level positive airway pressure ventilation maintains adequate ventilation in post-polio patients with respiratory failure. Acta Anaesthesiol Scand. 2006;50:580–5
160. Silbergleit AK, Waring WP, Sullivan MJ, Maynard FM. Evaluation, treatment, and follow-up results of post polio patients with dysphagia. Otolaryngol Head Neck Surg. 1991;104:333–8
161. Greninger AL, Naccache SN, Messacar K, Clayton A, Yu G, Somasekar S, Federman S, Stryke D, Anderson C, Yagi S, Messenger S, Wadford D, Xia D, Watt JP, Van Haren K, Dominguez SR, Glaser C, Aldrovandi G, Chiu CY. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis. 2015;15:671–82
162. Gralton J, Tovey E, McLaws ML, Rawlinson WD. The role of particle size in aerosolised pathogen transmission: a review. J Infect. 2011;62:1–13
163. Sehulster L, Chinn RYCDC; HICPAC. . Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003;52:1–42
164. American Institute of Architects. Guidelines for Design and Construction of Hospital and Health Care Facilities. 2014 Washington, D.C. American Institute of Architects Press
165. Lau JT, Fung KS, Wong TW, Kim JH, Wong E, Chung S, Ho D, Chan LY, Lui SF, Cheng A. SARS transmission among hospital workers in Hong Kong. Emerg Infect Dis. 2004;10:280–6
167. Hung LS. The SARS epidemic in Hong Kong: what lessons have we learned? J R Soc Med. 2003;96:374–8
168. Jewett DL, Heinsohn P, Bennett C, Rosen A, Neuilly C. Blood-containing aerosols generated by surgical techniques: a possible infectious hazard. Am Ind Hyg Assoc J. 1992;53:228–31
169. Angobaldo J, Marks M. Prevention of projectile and aerosol contamination during pulsatile lavage irrigation using a wound irrigation bag. Wounds. 2008;20:167–70
170. Tran K, Cimon K, Severn M, Pessoa-Silva C, Conly J. Aerosol-generating procedures and risk of transmission of acute respiratory infections: a systematic review. CADTH Technol Overv. 2013;3:e3201
171. Pshenichnaya NY, Nenadskaya SA. Probable Crimean-Congo hemorrhagic fever virus transmission occurred after aerosol-generating medical procedures in Russia: nosocomial cluster. Int J Infect Dis. 2015;33:120–2
172. Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, Hadler S, Pilishvili TCenters for Disease Control and Prevention (CDC). . Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014;63:822–5
173. Bennett N, Whitney CG, Moore M, Pilishvili T, Dooling KL. Use of 13-Valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61:816–9
174. Briere EC, Rubin L, Moro PL, Cohn A, Clark T, Messonnier NDivision of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC. . Prevention and control of Haemophilus influenzae
type b disease: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep. 2014;63:1–14
175. Centers for Disease Control and Prevention. . Estimates of deaths associated with seasonal influenza—United States, 1976–2007. MMWR Morb Mortal Wkly Rep. 2010;59:1057–62
176. Lindley MC, Horlick GA, Shefer AM, Shaw FE, Gorji M. Assessing state immunization requirements for healthcare workers and patients. Am J Prev Med. 2007;32:459–65
177. Poland GA, Tosh P, Jacobson RM. Requiring influenza vaccination for health care workers: seven truths we must accept. Vaccine. 2005;23:2251–5
178. Committee on Infectious Diseases. . Influenza immunization for all health care personnel: keep it mandatory. Pediatrics. 2015;136:809–18
179. Douville LE, Myers A, Jackson MA, Lantos JD. Health care worker knowledge, attitudes, and beliefs regarding mandatory influenza vaccination. Arch Pediatr Adolesc Med. 2010;164:33–7
180. Burls A, Jordan R, Barton P, Olowokure B, Wake B, Albon E, Hawker J. Vaccinating healthcare workers against influenza to protect the vulnerable—is it a good use of healthcare resources? A systematic review of the evidence and an economic evaluation. Vaccine. 2006;24:4212–21
181. Salgado CD, Farr BM, Hall KK, Hayden FG. Influenza in the acute hospital setting. Lancet Infect Dis. 2002;2:145–55
182. Sydnor E, Perl TM. Healthcare providers as sources of vaccine-preventable diseases. Vaccine. 2014;32:4814–22
183. Wicker S, Marckmann G. Vaccination of health care workers against influenza: is it time to think about a mandatory policy in Europe? Vaccine. 2014;32:4844–8
184. Thomas RE, Jefferson T, Lasserson TJ. Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions. Cochrane Database Syst Rev. 2013;7:CD005187
185. Kuster SP, Shah PS, Coleman BL, Lam PP, Tong A, Wormsbecker A, McGeer A. Incidence of influenza in healthy adults and healthcare workers: a systematic review and meta-analysis. PLoS One. 2011;6:e26239
186. Wicker S, Marckmann G. Influenza vaccination of healthcare personnel. Hum Vaccin Immunother. 2014;10:2627–8
187. Talbot TR, Schaffner W. On being the first: Virginia Mason Medical Center and mandatory influenza vaccination of healthcare workers. Infect Control Hosp Epidemiol. 2010;31:889–92
© 2016 International Anesthesia Research Society
188. Talbot TR. Update on immunizations for healthcare personnel in the United States. Vaccine. 2014;32:4869–75