Few healthcare workers would rank the common respiratory viruses first on a list of the diseases to which their work exposes them, but we would speculate that these illnesses cause more disruption and lost productivity than all the others we discuss combined.

Influenza The prototype of these illnesses is influenza. Influenza epidemics occur with distressing frequency within healthcare institutions, with predictable consequences; increased absenteeism or reduced efficiency of staff members and increased mortality, morbidity, and length of stay among the patients. Indeed, immunization of healthcare workers results in significantly reduced morbidity (43% reduction in influenza-like illness) and mortality (44% reduction) among geriatric patients in long-term-care facilities (9).

The capacity of influenza for explosive spread was demonstrated by an outbreak among 53 persons stranded aboard a grounded airliner for 3 hours: within 3 days, 72% of the passengers were ill with influenza A (10). When the “Asian” influenza A pandemic of 1957 reached the Oklahoma City Veterans’ Hospital, 19 (39%) of 49 patients on the neurologic ward were affected, three of whom died; all but one of the physicians on the ward were “incapacitated” (11). During the same epidemic, eight (62%) of 13 unvaccinated staff members studied at the New York Hospital developed influenza, as compared to 7 (35%) of 20 vaccinated staff (12). Influenza A/Bangkok (H3N2) produced illness in one third of patients and staff members on affected wards at a Chicago hospital (13). The same strain of influenza caused a 70% increase in absenteeism during a 2-week period among employees of a Winnipeg, Canada, hospital, which incurred excess sick-leave costs of $24,500 (1,980 Canadian dollars) (14). Reports of healthcare-associated outbreaks of influenza B appear to be less common than reports of influenza A. This finding may merely reflect the greater prevalence of influenza A, although one report of hospital surveillance during an influenza B epidemic found no clusters of disease despite 25 cases detected by culture (15).

Influenza is spread via infected nasopharyngeal secretions. Attempts in 1918 to transmit the pandemic strain failed because of improper technique; it was not until 1937 that Smorodintseff and associates demonstrated experimental transmission by droplets (16). Spread is believed predominantly to involve respiratory droplets, as well as direct person-to-person spread through contact with infected secretions. Airborne spread is possible, but not as well documented as with such diseases as tuberculosis and varicella. Mingling of the occupants, a vigorously coughing source patient, and a nonfunctioning ventilation system were associated with the airliner outbreak, and thus, it may have been entirely caused by droplet spread.

Given the opportunities for exposure to influenza during a community outbreak, the only realistic approach to prevention among healthcare workers is through immunization. Unfortunately, achieving high immunization rates among healthcare workers has proven difficult (17, 18 and 19), with rates often less than 50% (20). Hospital-wide influenza immunization programs that are highly publicized, bring the program to the worker, take advantage of social or peer pressure, and reward participation find greater success, but still fail to maintain vaccination rates above 90%. Mandatory influenza vaccination programs appear to have the greatest effect on sustaining acceptable influenza vaccination rates among healthcare personnel (21). In an established outbreak, cohort isolation may help prevent spread to other patients (22) but likely would be of little benefit to the work force, given the ubiquitous opportunities for exposure during an outbreak. The neuraminidase inhibitors have traditionally afforded protection against influenza A (H1N1, H3N2) and influenza B, should a worker at high risk of complications be unable or unwilling to participate in the immunization program. In recent years, however, some influenza A (H1N1) strains have become resistant to oseltamivir. A combination of oseltamivir with an adamantine or zanamivir alone may be used if prophylaxis is indicated. Current recommendations for the prevention and treatment of influenza are available from the Centers for Disease Control and Prevention (CDC) and should be consulted prior to prescribing antiviral therapy (23). Infected employees should not work in order to prevent spread to patients and others. (For more information on influenza, see Chapter 42.) (Note: All references to specific forms of isolation precautions, such as Standard, Droplet, or Airborne Precautions, refer to the “2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings,” by the Hospital Infection Control Practices Advisory Committee of the United States Public Health Service (24)) (see also Chapter 90).

Parainfluenza Parainfluenza infections are most problematic among infants and young children, and spread on pediatric wards is well documented. These outbreaks often involve the staff (25,26); an outbreak investigated at the Children’s Hospital National Medical Center was shown to affect six of 17 neonates along with 18 of 52 nursing personnel (26). Although the disease is relatively mild among older children and healthy adults, it can be a problem in long-termcare facilities, affecting both patients and staff, with patient deaths reported (27). Of the various strains of parainfluenza virus, type 3 appears to be implicated more often in healthcare-associated outbreaks. The spread of parainfluenza often is indolent (28), and the virus appears to be relatively hardy; droplets may contaminate environmental surfaces with virus that survives for many hours (29).

Spread of parainfluenza virus is by direct contact and by large droplets, which may create the potential for indirect contact spread. Airborne spread is plausible but has not been demonstrated. Immunity is not durable and reinfection occurs throughout life. Thus far, efforts to develop vaccines have not been fruitful. Thus, protection of the healthcare worker rests on identification and isolation of cases with use of Contact and, perhaps, Droplet Precautions.

Respiratory Syncytial Virus Respiratory syncytial virus (RSV) is the most important respiratory pathogen of infants and young children, in whom it is the predominant cause of bronchiolitis and pneumonia (30,31). Community-based outbreaks occur every winter and spring, and essentially the entire population has serologic evidence of infection by age 3 years. Immunity is short-lived and reinfection can occur annually. Thus, RSV spreads readily to healthcare workers. The disease is mild in previously infected adults, who may be asymptomatic or experience symptoms of the common cold (31). Despite their mild illness, however, infected healthcare workers can serve as a source of infection for pediatric (32,33) and other (27,34, 35, 36 and 37) patients in whom infection may be dangerous.

Hall et al. (32) studied healthcare-associated RSV during a community outbreak and found that 45% of infants hospitalized 1 week or more acquired infection as did 10 of 24 staff members. Indeed, in the absence of effective barrier precautions, 30% to 60% of healthcare workers caring for RSV-infected children acquired infection (38,39).

RSV infection appears to be acquired through inoculation of the eyes or nose by direct and indirect contact with infectious respiratory secretions (31,39). Use by caregivers of eye-nose goggles markedly reduces spread of the disease (38,40), probably by preventing selfinoculation via contaminated hands; others have shown similar benefit through use of gloves and gowns (41) or gloves, gowns, and masks (42). To curtail both direct and indirect contact spread, use of Standard and Contact Precautions is appropriate. As is so often the case, scrupulous hand washing is the key to prevention of infection (see also Chapter 91).

Adenovirus The adenoviruses are responsible for a variety of syndromes: typical upper respiratory infections (e.g., cough, coryza, pharyngitis), particularly of children; febrile acute respiratory disease of military recruits; epidemic keratoconjunctivitis; pharyngoconjunctival fever; and, uncommonly, pneumonia (43). Spread can be explosive, particularly in closed groups, such as military recruits or shipyard workers.

A number of outbreaks of epidemic keratoconjunctivitis have been documented in healthcare facilities. Most often, these outbreaks involve spread to patients exposed to contaminated ophthalmologic equipment or solutions or to a caregiver’s unwashed hands (44, 45, 46, 47, 48, 49, 50, 51 and 52). Healthcare workers have acquired conjunctivitis not only through care of patients with conjunctivitis but also through care of patients with other adenovirus infections such as pneumonia (53) when appropriate isolation precautions were not observed (see also Chapter 90).

Although less common, outbreaks of respiratory disease resulting from adenovirus are more serious. A 1980 outbreak at Children’s Hospital in San Diego, California, involved six patients (of whom four died) as well as 300 (78%) of 383 employees, of whom 15% developed conjunctivitis, 28% diarrhea, and 72% upper respiratory symptoms (53a). The outbreak was terminated by strict isolation, cohorting, furlough of ill employees, and closure to new admissions. A smaller but similar outbreak in a neonatal intensive care nursery resulted in two patient deaths and infection of nine patients and ten staff members (54). An outbreak in a pediatric long-term-care facility resulted in 11 deaths and 28 cases (46% attack rate) among patients; 22% of staff members (23 of 106) acquired illness (55). An outbreak in another pediatric long-term-care facility following infection in one infant spread to involve two staff members and 10 (30%) of 33 patients, of whom two died (56).

Although respiratory illness is rarely serious among adults, it may be more severe among residents of longterm-care facilities (27,57). The infection can be fatal among the immunocompromised (58). Serotype 14 has recently emerged and may be associated with more severe respiratory illness, even among the less infirm. An outbreak of severe respiratory disease in a military training facility affected 48% of trainees (551/1147), resulting in 23 hospitalizations (4 requiring admission to an intensive care unit [ICU]) and one death (59).

Good evidence supports the spread of adenovirus by direct contact, indirect contact, droplets, and (predominantly among children) the fecal-oral route. Airborne spread is plausible, but we are not aware of a healthcareassociated outbreak that cannot be explained by contact or droplet spread. Airborne spread does not appear to be necessary to explain epidemics among military recruits (59,60), given their prolonged close contact and the opportunity for droplet spread. Contact Precautions should be used for patients with adenovirus conjunctivitis; Droplet Precautions should be added for those with adenovirus respiratory infection. Environmental decontamination can be difficult, because the adenovirus is unusually hardy; alcohol and chlorhexidine are not reliable agents for disinfection (61). A variety of vaccines have been used with success in the military, but none is available for civilian use (see also Chapter 48).

Rhinovirus and Coronavirus The rhinoviruses and coronaviruses cause the common cold—coryza, with variable cough, and pharyngitis. More than 100 serotypes of
rhinovirus are known (virtually ensuring the opportunity each year to encounter a virus to which one is not yet immune), as well as an as-yet-undetermined number of coronaviruses. Although the rhinoviruses and the usual coronaviruses are virologically distinct, they are clinically and epidemiologically similar enough to be considered together. Widespread community outbreaks caused by these viruses occur every winter, with low-level spread throughout the year. As every parent knows, incidence rates are highest among young children and decline with increasing age among adults (apart from a higher incidence among adults with young children). Schools and homes are the major foci of dissemination (62). Given the ubiquitous opportunities for exposure and the usually benign outcome, healthcare workers may not view the common cold as a target for infection control. The frequency of infection, though, is not trivial. In a prospective analysis of healthcare workers with respiratory illness, nearly 40% were found to be infected with rhinovirus. Of those infected employees, one quarter provided care for high-risk patients (63).

Transmission does occur between patients and caregivers, however, with outcomes that are burdensome for caregivers and potentially serious for selected patients, such as the immunocompromised, the very young (30), or the elderly (64). For example, Valenti et al. (33) investigated an outbreak of viral respiratory disease in a neonatal intensive care unit (NICU) and determined that one half of the cases were caused by RSV and one half were caused by rhinovirus; respiratory illnesses were similarly serious in the two groups of infants (33). The investigation showed that the infants acquired their infections from their caregivers, 31% of whom had been ill in the preceding week. Unlike other viral respiratory infections, rhinovirus infections do not appear to be significantly more dangerous among the healthy elderly (27), although lower respiratory tract involvement has been seen (65) and can have severe consequences among those with chronic pulmonary disease (64).

During infection, rhinovirus is present in high titer in nasal secretions but only in low titer, if at all, in oral or pharyngeal secretions (62). Volunteer studies have shown that infection is acquired readily via the nose or conjunctiva but poorly via the oral route. Although the virus is relatively hardy and can survive drying on environmental surfaces for several hours, the overwhelmingly most important route of spread is nose to hand to nose or eye. Prevention of spread of infection to or from workers is best accomplished through use of Standard Precautions, with particular attention to hand washing. Workers should be encouraged to stay home at times of profuse catarrh.

Severe acute respiratory syndrome (SARS) emerged in southern China late in 2002 and spread rapidly to Hong Kong, Singapore, Taiwan, Vietnam, and Canada (66). Few cases were documented in the United States. A new coronavirus was quickly established as its cause. Although definitive information concerning the nuances of transmission is lacking, it is clear that droplet and close contact spread occur, sometimes with astounding efficiency from socalled super-spreaders. Aided by a large, distinctive, and malfunctioning sewage system, transmission from virus excreted in feces may have occurred in a high-rise housing complex in Hong Kong. The role of conventional fecal-oral transmission and the role of environmental contamination remain uncertain.

Healthcare-associated transmission to healthcare workers (with some fatal results) was a prominent feature in virtually every country experiencing the disease (66, 67, 68, 69, 70 and 71). The United States was spared almost all healthcare-associated spread. This may have been the happy consequence of intensive education by the CDC, the good fortune of not having a super-spreader enter the country, or other unknown factors.

Much of the healthcare-associated spread of SARS was attributed to inconsistent observance of strict Airborne Precautions and inconsistent use of personal protective equipment, particularly during aerosol-generating activities. Droplet Precautions have been shown to be effective in reducing transmission risk. If SARS recurs, the fastidious use of isolation and personal protective equipment will be critical to avoiding spread of the virus to healthcare professionals.

Coxsackievirus, Echovirus, Poliovirus, and Miscellaneous Enteroviruses The enteroviruses cause a variety of syndromes, including aseptic meningitis, encephalitis, poliomyelitis, herpangina, epidemic myalgia, upper and lower respiratory disease, hand-foot-mouth disease, conjunctivitis, pericarditis, and myocarditis (72). In the United States, enterovirus infections occur almost exclusively between May and November, peaking in the summer months (73). Many enterovirus infections are associated with exanthems. These viruses are so common, and their manifestations so varied, that recognition of transmission or identification of the causative agent often occurs only when a distinctive outbreak occurs.

Enterovirus infections are common in children, for whom they are generally mild. Infections are more likely to be serious among infants and adults, who experience a greater frequency of cardiac or neurologic involvement (72). For example, an outbreak of echovirus 30 in a daycare center came to attention when 13 parents developed aseptic meningitis (74). Similarly, in an outbreak of coxsackievirus B5 infection in a newborn nursery, illness was sporadic and mild among full-term infants but more prevalent and severe among premature infants; two nurses developed severe pleurodynia and fever (75). A New Zealand hospital experienced a dual outbreak involving echovirus 11 and coxsackievirus B3 (76). Eleven infants and 12 staff members developed meningitis; about one-half the infections were healthcare associated. Modlin (77) reviewed 16 nursery outbreaks of echovirus and found hospital personnel to be involved in nine cases. In a unique outbreak of hand-foot-mouth disease in Utah, 17 (13%) of 136 operating suite personnel—but no patients—developed clinical disease resulting from contact spread following illness in an index surgical technician (78).

All enteroviruses reside in the gastrointestinal tract, and thus most spread is by direct contact involving the fecal-oral route. Standard Precautions should be supplemented by Contact Precautions for diapered or fecally incontinent individuals. Although many of these viruses
can be recovered from the oropharynx during illness and have been experimentally transmitted by coughing (72), use of Droplet Precautions is not routinely recommended. As always, hand washing is likely the most important single preventive strategy.

Poliovirus infection has been eradicated from the Western Hemisphere (79). Until worldwide eradication is achieved, occasional imported cases may be seen in the United States. However, the risk of spread will remain confined to sects that shun immunization unless immunization efforts wane in this country. The use of live attenuated oral poliovirus vaccine (OPV) has been abandoned in the United States. The risk of vaccine-associated disease was once seen at a rate of about one case per 2.6 million doses (80). In countries where OPV is still used, a risk of vaccine-associated paralytic disease exists in contacts of OPV recipients, raising a theoretical concern of infection in a healthcare worker, although we find no evidence that such an event has ever occurred. In addition, transmission should be prevented by Standard Precautions. Thus, verification of primary poliovirus immunization of healthcare workers is recommended only for (a) those working with poliovirus in the laboratory; (b) those who might care for, or handle specimens from, a patient excreting wild poliovirus; or (c) in the event of an outbreak (see also Chapters 24 and 50).

Rotavirus, the Norovirus, and Related Viruses Rotavirus is the principal etiologic agent of infantile diarrhea and is responsible for up to one half of all episodes of acute diarrheal disease in infants and young children. The Norwalk-like viruses, a growing group of similar yet genetically diverse members of the Caliciviridae, consist of Norovirus (formerly, Norwalk virus) and a host of other small (27 nm, as compared to 70 nm for rotavirus) round-structured viruses (SRSVs) such as the Snow Mountain, Hawaii, and Marin County agents (81). These agents appear to be responsible for two-thirds of all nonbacterial gastroenteritis (82). An additional but much smaller proportion of viral gastroenteritis is attributable to the astroviruses, other caliciviruses, and minireoviruses. The coronaviruses (especially including the toroviruses (83)), adenoviruses, enteroviruses, and parvoviruses, discussed elsewhere in this chapter, can also cause gastroenteritis.

Several healthcare-associated outbreaks of rotavirus have been documented in neonatal or pediatric units, usually initiated by admission of children involved in a community outbreak (84, 85, 86, 87, 88, 89, 90 and 91). Although each of these outbreaks involved substantial healthcare-associated spread of infection to hospitalized infants and children, no healthcare workers were reported to acquire illness. Several rotavirus outbreaks among geriatric populations have also been reported (92, 93 and 94). In contrast to the experience with pediatric outbreaks, infection and illness occurred among staff members in each of these geriatric outbreaks. Another outbreak, involving somewhat less-elderly patients on a cardiology ward, also involved the staff (95), as did an outbreak on an obstetrics unit (96). Whether this difference in likelihood of illness among staff members reflects random chance, differing host adaptation of viral strains, or systematic differences in infection control practices is unclear. Routine use of rotavirus vaccine in infancy will reduce the likelihood of the introduction of these viruses into healthcare facilities.

Rotavirus is spread by the fecal-oral route, principally via the hands of healthcare workers. The virus is highly stable, but environmental contamination does not appear to be an important pathway of transmission in an outbreak. Similarly, despite occasional isolation of the virus from pharyngeal secretions, airborne spread does not appear likely. Standard Precautions should be sufficient, supplemented by Contact Precautions for diapered or incontinent patients. Of interest, quaternary ammonium disinfectants appear to be ineffective against rotavirus; bleach or phenolics should be used if rotavirus environmental contamination is a concern (97). (For additional information on enteric viruses, see Chapters 24 and 50.)

Noroviruses and other SRSVs cause explosive outbreaks of gastroenteritis in the home, school, community, and nursing home settings, particularly in the winter and spring. The gastroenteritis is marked by sudden onset of vomiting and diarrhea. Rates of secondary spread are high, and disease often involves school-aged children, parents and caregivers, and some young children. Of 270 outbreaks reported to the CDC from July 2000 to June 2004, 31% involved nursing homes and hospitals (98). In a Tennessee outbreak, 55% of patients and 61% of the nursing staff in a long-term-care hospital became ill in a 10-day period (99); an outbreak in a similar facility in Los Angeles involved 55% of residents and 25% of staff members (100). Although attack rates have been higher among patients than staff in most outbreaks, this outcome is not always the case. In a recent North Carolina outbreak, 31% of staff and 11% of patients were ill (101). A 3-week outbreak at a 600-bed Toronto, Canada, hospital involved 27% of the 2,379-person staff, as well as 10% of their household contacts (102). The outbreak appeared to be centered in the emergency room, where 69% of the staff and 33% of visitors acquired illness; an extensive investigation suggested spread of infection by the airborne route. Investigation of a cruise-ship outbreak the following year similarly suggested a role for airborne or droplet spread (103). Investigators of several subsequent outbreaks have concluded that airborne or droplet transmission occurred (100,104, 105 and 106), although some commentators remain skeptical (81,107). Caul (108) has pointed out that, based on electron micrographic studies, each ounce of vomitus contains 30 million viral particles; only 10 to 100 are required to cause infection. Projectile vomiting associated with Norovirus gastroenteritis may aerosolize infectious droplets. This view is supported by data such as those of Chadwick and McCann (104), who found that staff members exposed to nearby vomiting had a fourfold elevated risk of illness; nearby vomiting and close patient contact remained as the only significant independent predictors in a multiple logistic regression. Numerous outbreaks were reported to the CDC in 2006 to 2007, especially in long-term-care facilities. Two newly identified cocirculating norovirus strains that emerged in 2006 likely accounted for the increased burden of disease (109,110).

The appropriate choice of isolation precautions for Norovirus and related gastroenteritis is somewhat contentious; Standard Precautions may not be sufficient. Although unproven, the plausibility of Droplet spread and the epidemiologic evidence supporting that route of transmission appear to be sufficient to warrant Droplet Precautions when confronted by forceful vomiting caused
by Norovirus-like agents. The evidence that environmental contamination plays a role in disease transmission is insufficient to recommend Contact Precautions, although, as is recommended for rotavirus, Contact Precautions should be considered in the event of fecal incontinence or other gross soiling. Healthcare-associated outbreaks may require cohorting and furloughing of involved staff members until they are well; most affected institutions have employed elaborate environmental decontamination, the need for which is unproven, but perhaps prudent (see also Chapters 24 and 50).

Hepatitis A The hepatitis A virus causes an acute, selflimited infection whose clinical manifestations vary with age. Children typically experience mild or no illness; adults commonly develop malaise, nausea, vomiting, and icterus. Fulminant hepatitis and death are rare (0.1-0.5%) (111). The disease is clinically indistinguishable from several other viral hepatitides, and serologic diagnosis is required.

Healthcare-associated transmission is thought to be unusual. Most healthcare-associated outbreaks arise following admission of a patient not suspected to have hepatitis A, who either has subclinical infection, is in the prodrome, or is serologically false negative because of immune deficiency (112), emphasizing the need to follow Standard Precautions for all patients. For example, three physicians caring for a 21-month-old girl with unsuspected anicteric hepatitis A became infected and ill; another developed subclinical infection (113). Of 58 susceptible workers exposed to a patient who had vomiting, diarrhea, and fecal incontinence during the 8 days preceding jaundice, six (10.3%) acquired infection (114). An outbreak in one NICU affected 13 infants, 22 nurses, 8 other staff, and four household contacts (115); an outbreak in another NICU involved four infants and ten staff members. Investigations of such outbreaks have repeatedly identified two sets of behaviors as risk factors for worker infection: (a) a failure to wash hands, wear gloves, or both (114, 115 and 116); and (b) eating, drinking, or smoking in the patient care unit (115,117,118).

Hepatitis A is transmitted almost exclusively by the fecal-oral route. A brief viremic phase occurs, during which blood-borne transmission is possible; airborne transmission has been alleged in at least one report (119) but is unlikely. The virus is present in high concentrations in the stool, and Standard Precautions should be supplemented with Contact Precautions in the case of fecal incontinence (including diapered infants).

Excellent vaccines have been developed and licensed. Although considered indicated among US healthcare personnel only for susceptible individuals in areas where hepatitis A is highly endemic (120), cost-benefit analyses have suggested that the cost of hepatitis A vaccination in healthcare workers, per life-year saved, was similar to that of other standard medical interventions (121) (see also Chapter 46).

Infections caused by the herpes viruses are among the most common diseases of humans. The herpes viruses are not cleared following primary infection but, rather, reside permanently in target tissue. The viruses remain capable of reactivation, which might result in clinical disease on a regular basis (herpes simplex), occasionally (varicella zoster virus [VZV]), or only in the face of immune compromise (cytomegalovirus [CMV]). The herpes viruses have been incriminated as risk factors for several neoplasms, and those that are lymphotropic alter immune function during active infection.

Herpes Simplex Virus Herpes simplex virus (HSV) infection is common. In the United States, by age 45, 70% to 80% of the population has acquired antibody to HSV-1, the strain associated with oral lesions; 15% to 20% of whites and 40% to 60% of blacks have antibody to HSV-2, the strain associated with genital lesions. Infection with either strain is lifelong; following primary infection, the virus travels along sensory nerves and becomes latent within sensory ganglia. In a recurrence, the virus reactivates, travels peripherally from the ganglia along the nerves, and reestablishes cutaneous infection (122). Of importance to the healthcare worker, active virus can also be demonstrated in oral or genital secretions when no cutaneous or mucosal lesion is evident.

Although herpes virus can cause a variety of clinical syndromes, only one is routinely of pertinence to the healthcare worker: whitlow, a term derived from the middle-English whit flaw, or a flaw in the quick of the nail. Both HSV-1 and HSV-2 can cause whitlow; prior oral or genital infection does not necessarily protect one from acquiring a new infection of the finger (123). Workers with frequent exposure to oral secretions, such as dental workers, respiratory care personnel, and anesthesia staff members, are at greatest risk (124, 125, 126, 127 and 128). Oral transmission can occur during mouth-to-mouth resuscitation (129), and at least one outbreak has been reported involving transmission between nurses and patients in a pediatric ICU with further household spread (130).

Under most circumstances, compliance with Standard Precautions should ensure protection from infection with HSV. Workers should glove (both hands) before contact with any oral secretions, including before airway suctioning. Contact Precautions should be considered when dealing with neonatal, disseminated, or severe primary herpes infection (see Chapter 44). Workers with whitlow should be restricted from contact with patients or their environment, and restriction from contact with high-risk patients may be appropriate for workers with orofacial herpes lesions.

Varicella Zoster Virus The VZV is the etiologic agent of chickenpox; reactivation of the latent virus in previously infected persons produces the disease known as herpes zoster (shingles). Chickenpox is common among children, in whom the disease is generally mild; severity of illness increases with age of the subject. Despite repeated epidemics in schools, a small proportion of adults escape childhood infection and remain susceptible. Nearly all healthcare workers (98-100%) with a clinical history of chickenpox are immune as measured by serology (131), but 4% to 47% (median, 15%) of those with a negative or uncertain history of prior chickenpox are susceptible (131). In one study, the rate of susceptibility was higher among those <35 (7.5%) than those more than 35 years of age (0%) (132). Primary infection in susceptible adults can (but usually does not) cause serious disease, including varicella pneumonitis,
which can be fatal. Two groups are at special risk from primary varicella infections: the immunocompromised, among whom the mortality rate may approach 20%; and newborns whose mothers develop primary infection from 5 days before to 2 days after giving birth. The combination of absent transplacental antibody and massive exposure places these infants at high risk, and the mortality rate can approach 30% (133).

Countless healthcare-associated outbreaks of VZV infection have been reported; indeed, it would be surprising to learn of a hospital caring for pediatric patients that has been spared. The high communicability of VZV, the routine presence in the hospital of immunocompromised patients at risk of serious or fatal disease if infected, and the presence of a core of susceptible healthcare workers make the management of VZV exposure one of the most challenging tasks of the infection control worker. This task is complicated by the fact that VZV is one of the few agents of healthcare-associated infection capable of true airborne spread (134, 135, 136, 137, 138, 139, 140, 141 and 142). Airborne spread of VZV can arise from patients (or personnel) with primary infection (141), from patients with disseminated zoster (136, 137 and 138), or rarely from patients with localized zoster (140). Of course, the infection can be transmitted by contact as well as through the air.

Management of VZV exposure incidents is burdensome and expensive. In a 1-year period at their hospital, Krasinski et al. (143) recorded 95 VZV infections (93 inpatients, two staff members), resulting in six exposure incidents involving 156 patients and 353 staff members. Fifty-one patients and 101 staff members denied prior VZV infection, but serology confirmed 5 and 11, respectively, to be susceptible. Three secondary infections occurred, six courses of varicella zoster immune globulin (VZIG) were administered, and 13 staff members were furloughed, at a cost of 356 hours of infection control staff time and $41,500. Similarly, Weber et al. (144) documented exposures in 121 patients and more than 300 staff members in a single year, of whom 11 and 49, respectively, were serosusceptible; costs of managing these exposures totaled $55,934. Given the frequency of VZV exposure incidents and the burden they impose, it is not surprising that the appropriate management of exposure events has been much debated (137,145, 146, 147, 148, 149, 150, 151, 152, 153 and 154).

Immunization of susceptible employees is now the cornerstone of the varicella control program and is cost effective (131,155,156). Susceptible employees can be identified by serotesting all employees, serotesting only those with a negative or uncertain history of chickenpox, or by foregoing serotesting and simply immunizing all those with a negative or uncertain history; the choice of strategy will depend on the institution’s assessment of the relative costs of vaccine and serology, the rate of seronegativity in its employees, and the risk it is willing to accept of missing the detection and vaccination of a susceptible person (131,157).

Immunization of staff does not address all concerns. Although seroconversion is not ensured following vaccination, postvaccination serology is not helpful and is not recommended (120). In addition, vaccinees can develop a mild generalized rash and may pose a risk of infection to susceptible patients. The institution should develop policies concerning management of vaccinated employees who develop a rash illness or who are subsequently exposed to varicella. Employees with chickenpox, as well as immunosuppressed employees with zoster, must be excluded; otherwise, healthy employees with covered zoster lesions may work, except with high-risk patients.

When an exposure event occurs, unvaccinated susceptible employees with exposure (i.e., those who have provided care without the required precautions) are furloughed from the 8th to the 21st days following exposure (120). Only employees known to be immune are assigned to care for patients with active VZV infection. Contact Precautions are used for all patients with VZV infection, and Airborne Precautions are added for those with primary varicella or disseminated zoster. Finally, exposed susceptible patients are discharged as soon as possible; if not discharged by the 8th day following exposure, they are placed in isolation through the 21st day or until discharged. VZIG is considered for exposed susceptible persons with impaired immune responses, including pregnant females (see also Chapter 43).

Epstein-Barr Virus The Epstein-Barr virus (EBV) is the principal causative agent of infectious mononucleosis and has been implicated as a cause of Burkitt’s lymphoma and nasopharyngeal carcinoma. From 30% to 95% of children have antibodies to EBV by age 6; the proportion is higher in less-developed countries. After children, young adults are the most commonly infected group, in whom infection is more likely to be symptomatic (158).

Transmission appears to require exchange of saliva and otherwise does not occur even with prolonged close contact. Few reports suggest healthcare-associated spread. Ginsburg et al. (159) reported an outbreak of infectious mononucleosis at an outpatient clinic in which five (17%) of 29 staff members developed clinical disease with serologic confirmation of recent EBV infection. The only possible route of transmission identified by the authors was the communal use of poorly washed coffee cups. One additional report noted the development of mononucleosis, reported to be serologically confirmed, in five (17%) of 29 laboratory workers; three had been involved in performing mononucleosis tests on serum specimens.

EBV is apparently transmitted rarely, if ever, in the healthcare setting, and no supplement to Standard Precautions is indicated in the care of patients infected with EBV.

Cytomegalovirus Nearly everyone acquires CMV infection at some point in life; age at first infection follows a pattern similar to that previously described for EBV, with larger proportions of children infected earlier in life in lessdeveloped countries. Infection is most often asymptomatic or associated with nonspecific symptoms, but in less than 1% of cases may cause mononucleosis, hepatitis, or respiratory, gastrointestinal, or neurologic disease. As with the other herpes viruses, CMV infection is lifelong, and subsequent immunocompromised permits the virus to reactivate and cause respiratory, gastrointestinal, ophthalmologic, or other disease. In addition, CMV is one of the five classic teratogenic infections; primary or subclinical recurrent maternal infection during pregnancy can cause transplacental infection and neurologic damage to the fetus. Most fetal infections result from recurrent, rather than primary,
maternal infection; the risk of fetal infection is about 1% for pregnant women with CMV antibody (160).

Concern regarding fetal CMV infection has stimulated substantial anxiety among healthcare workers, although to our knowledge, no healthcare-associated outbreak of CMV has ever been reported. Numerous studies of seroprevalence and seroconversion rates have been performed among nurses and other staff members who care for young children (161,162,163,164, 165, 166, 167, 168, 169, 170 and 171); although some studies found some elevation in risk (often not reaching statistical significance), none concluded that healthcare workers incurred a material additional risk as compared to the risk associated with routine home and community life. In recent years, anxiety concerning CMV appears to have subsided. This reaction may reflect reassurance by the cited data and by the adoption of Standard Precautions—or perhaps distraction by other concerns such as HIV and pandemic influenza. CMV is excreted in urine and saliva, as well as stool, tears, breast milk, semen, and cervical secretions (160). Droplet or airborne spread does not appear to occur, even during mechanical ventilation (172). Adherence to Standard Precautions is adequate to protect the worker (see also Chapter 45).

Human Herpesviruses 6-8 Human herpesvirus 6 (HHV-6) has been identified as the causative agent of roseola infantum (also known as exanthem subitum and sixth disease). Roseola, the last of the classic exanthems of childhood to be differentiated, occurs commonly in children between the ages of 6 months, after waning of maternal antibody, and 4 years, by which age almost all children are seropositive. Within this age range, HHV-6 is a common cause of febrile illness, accounting for 20% of emergency room visits by infants 6 to 12 months old (173). Reactivation during the year or two following primary infection was found in 16% of subjects (173), and the occurrence of occasional outbreaks (174) suggests that reinfection of children is possible. Primary infection of adults is rare, because most acquire immunity in childhood, but when it occurs, it can produce lymphadenopathy, hepatitis, or a mononucleosislike syndrome (175). Serious or fatal HHV-6 reactivation has been demonstrated in recipients of bone marrow and, to a lesser extent, liver transplants. However, no evidence of transmission to healthcare workers exists as yet; thus, no infection control measures beyond Standard Precautions are needed. Serologic studies show that infection with human herpesvirus 7 is widespread in childhood. The virus may be another cause of roseola infantum; otherwise, its clinical significance is uncertain. Human herpesvirus 8 seems to resemble EBV in its ability to transform lymphocytes, and appears to be important in the cause of Kaposi’s sarcoma (176) and has produced bone marrow failure in patients with kidney transplants (177). Standard Precautions are indicated.

Herpesvirus Simiae Herpesvirus simiae, also known as simian herpesvirus B, is enzootic in rhesus, cynomolgus, and other macaque monkeys in whom it behaves much as HSV-1 does in humans. The disease can be transmitted to humans by the bite of a monkey; of 23 patients known to have symptomatic infections prior to 1987, 18 died of encephalitis. Only one known instance of spread from human to human has been reported, but it is noteworthy for occurring in the course of providing nursing care: the wife of a monkey handler repeatedly applied cortisone cream both to her husband’s wound and to her own excoriated dermatitis; he died, but she received acyclovir and her disease did not progress (178). Standard Precautions appear to be sufficient to prevent transmission to the healthcare worker (179).

Measles Measles, perhaps the most contagious disease extant, is an acute exanthematous infection caused by the rubeola virus (180). It has been known since ancient times and was ranked first among the exanthems by the 19th-century nosologists (181). Illness begins with cough, coryza, and fever; an enanthem (Koplik’s spots) and a maculopapular exanthem follow. Measles is the most dangerous of the common exanthematous diseases of childhood. Even in healthy children, the disease can progress to pneumonia or, less commonly, encephalitis; bacterial pneumonia can also complicate the course. Chronic complications include subacute sclerosing panencephalitis. Measles infection is more serious in adults and in immunocompromised individuals. A safe, effective live attenuated vaccine exists, and its widespread use has interrupted the endemic transmission of measles in the United States (182).

The exceptional communicability of measles permitted continued epidemics in past years, despite relatively high immunization levels. Measles outbreaks typically involve one or both of two groups: (a) infants too young to be immunized and young children who escaped immunization, and (b) young adults (including healthcare workers) with primary vaccine failure (about 2-5% of vaccinees). These problems have been addressed with substantial success by vigorous immunization campaigns (183) and by implementing a two-dose immunization schedule, which gives a second opportunity to immunize those who failed to seroconvert when first vaccinated (184,185). History makes it clear, however, that any slippage in immunization rates will lead to a resurgence of measles consequent to importations from areas of the world where active transmission continues (182).

Reports of measles infections among healthcare workers caused by healthcare-associated outbreaks once were frequent (185, 186, 187, 188, 189, 190, 191, 192, 193, 194 and 195), and the frequency of such events climbed during the 1980s. For the 5-year period 1980 to 1984, 241 cases of measles (1.1% of all cases from 1980 to 1984) were acquired in healthcare settings; of the 241 cases, 24% were among staff members (188). In the next 5-year period, 1,209 medical-setting cases were identified (3.5% of all cases during the period); 28% of the infections occurred in staff members (187). Most of these cases represented a failure to immunize, not a failure of vaccine; only 20% of staff members for whom immunization status was known were documented to have received even one dose of vaccine. From 1985 through 1991, 2,997 measles cases were acquired in medical facilities, representing 4% of the total in that period (196). As measles has been brought under greater control, the mean age of patients has shifted upward (27% of cases from 1993 to 1995 were in persons older than 20 years of age), and the proportion of cases acquired in medical settings increased (to 14% for the
period 1992-1995) (197). In the United States, healthcareassociated acquisition of measles by healthcare workers in the 21st century has been essentially eliminated.

Healthcare-associated measles was a serious matter, involving substantial risk to patients and staff. During 1988, Children’s Hospital in Los Angeles admitted 37 patients with measles (193). Six cases were unsuspected, exposing 107 patients and 24 staff members. Twelve patients and seven employees developed measles; one patient died, and two workers were hospitalized with pneumonia. Eight hundred workers required vaccination, and 211 workdays were lost. Others have recounted the disruption and expense associated with these outbreaks (190,192,198). In addition to jeopardizing healthcare workers and inpatients, healthcare-associated outbreaks can play an important role in propagating measles in the community (191,193,199,200).

Like varicella, measles is spread readily by the airborne route. In 1937, Wells placed ultraviolet lights in selected classrooms of two schools (6). In a subsequent measles epidemic, the attack rate was dramatically higher in the control classrooms, indicating causation of measles by an airborne agent susceptible to inactivation by ultraviolet light. Analyses of other outbreaks have confirmed the potential for airborne spread (194,201,202), and Airborne Precautions should be used for patients known or suspected to have measles. Isolation strategies, however, clearly do not eliminate the risk of healthcare-associated measles; healthcare workers must be immune. Authorities now are willing to categorize as immune all persons born before 1957 (196,197,203, 204 and 205). From 1985 through 1991, 29% of healthcare workers reported with measles were born before 1957. Numerous serosurveys support the view that persons in this older group are less likely to be susceptible than younger persons (206, 207, 208, 209, 210, 211 and 212). Thus, because of the absence of endemic measles in the United States today, the 1957 demarcation is practical.

Immunization program costs can be minimized by devising program strategies that optimize the balance between obtaining preimmunization serology (to immunize only the susceptible) and immunizing without serology (a less expensive alternative if most will need immunization) (180,207,213,214). The ideal measles prevention program would require that regardless of age, every worker with patient contact show documentation of receipt of two doses of measles vaccine after the first birthday, at least 1 month apart, or serologic evidence of immunity. Immunization would be required, as necessary, to satisfy this standard. However, substantial practical difficulties are encountered with this approach. Many workers properly immunized in childhood cannot document that fact and, thus, would require either serologic screening or two immunizations. If serologic screening is pursued, rubella immunity also should be assayed; more workers are susceptible to rubella than to measles (205), and primary vaccine failure could have occurred with either antigen. Finally, a program incorporating serologic screening incurs substantial overhead associated with tracking of results and recall of employees.

The CDC’s Advisory Committee on Immunization Practices (ACIP) recommended in June 2009 that all healthcare workers born after 1956 be required to provide laboratory evidence of immunity, laboratory confirmation of disease, or documented proof of receipt of two doses of vaccine; those born before 1957 should be considered for two doses of vaccine without proof of immunity (215). In an outbreak of measles, two doses of MMR vaccine is recommended for those born before 1957 who lack laboratory evidence of immunity. A simpler alternative approach is to give one injection of combined measles-mumps-rubella (MMR) vaccine to every employee who cannot document immunity or adequate prior immunization. Although this approach is not as comprehensive as the ideal program, the shortfall in immunization coverage would be limited to those persons who were susceptible to measles prior to this immunization, who failed to respond to this immunization, and who would have responded to a second injection given a month later. Data from Willy et al. (211) suggest that this strategy would leave 0.7% more of the work force susceptible (or equivocal) than would the ideal program (6.1% initially susceptible, 14.1% nonresponders to first vaccination, 81.8% responders to second vaccination). In comparison, programs that do not immunize persons born before 1957 leave 1.6% (211) to 6.4% (206) of employees susceptible; those that immunize only new hires can be expected to have substantial numbers of susceptible employees for many years.

Regardless of program strategy, MMR vaccine should be used. As discussed later, the consequences of healthcareassociated rubella can be disastrous, and many healthcare workers remain susceptible to mumps. No ill effects ensue from immunizing those already immune, and persons not yet immune require immunization. Individuals responsible for employee immunization programs will find helpful the previously cited program analyses (209,210,216,217), the analysis of vaccine response by Willy et al. (211), and the detailed recommendations published in a 1994 consensus paper (218) and recommendations provided by the ACIP (215) (see also Chapter 75).