Healthcare-Associated Measles, Mumps, Rubella, and Human Parvovirus B19
Kathleen M. Gallagher
Preeta K. Kutty
Eileen Schneider
Jane F. Seward
Healthcare-associated measles and rubella are well recognized and have been the cause of substantial morbidity among both patients and hospital workers. Immunocompromised patients and healthcare personnel (HCP) are particularly vulnerable to severe infections and even death with some of these diseases. Because of highly successful vaccination programs that resulted in an interruption of endemic disease transmission and the elimination of measles and rubella in the United States, measles and rubella are no longer primarily childhood diseases (1,2). However, children may still acquire measles or rubella, particularly if they travel abroad and are unvaccinated or live in communities with lower rates of vaccine coverage and/or pockets of unvaccinated persons (3,4). Because of the severity of measles, patients frequently access medical care and may expose HCP to the disease in emergency rooms or in hospitals. In 2008, the United States experienced the largest healthcare-associated measles outbreak in more than two decades with seven cases acquired in hospital settings, including one case in an unvaccinated HCP following the hospital admission of an adult foreign visitor with measles (5). Healthcare-associated outbreaks of rubella have not been reported in the United States since its elimination was declared; however, HCP in the United States remain at risk for exposure to cases of imported rubella. Mumps outbreaks are not commonly described in hospital settings, probably because of the lower complication rate of mumps compared with measles; nevertheless, during community outbreaks, HCP in hospitals may be exposed to mumps (6). The transmission and impact of parvovirus B19 in hospital settings are less well understood, though outbreaks in hospital settings involving adult patients as well as HCP have been described. Patients with erythema infectiosum are likely to be infectious before, and not after, the onset of clinical manifestations, and persons who are immunocompromised with a chronic B19 infection can be infectious for prolonged periods. Vertical transmission of B19 infection from mother to fetus has also been documented (178). Understanding the transmission, infectiousness, and at-risk populations of parvovirus B19 is critical to prevention and control.
HCP are at risk for exposure to each of these viral diseases, and if susceptible, may transmit these infections in healthcare settings. This draws attention to the critical need for comprehensive prevention and control programs. One important component of such programs is providing basic education to HCP on the modes of transmission of these nosocomial pathogens and methods of prevention and control.
Integral to any prevention and control efforts are systematic screening and vaccination programs for HCP, prompt diagnosis and management of potentially transmissible illnesses or exposures among hospital workers, and the implementation of patient management techniques that lower the risks of transmission (Table 51-1).
All medical institutions (inpatient and outpatient, private and public) should ensure that all HCP who work within their facilities (i.e., medical or nonmedical, paid staff, student or volunteer, full time or part time, with or without patient care responsibility) have evidence of immunity to measles, mumps, and rubella (Table 51-2). A comprehensive program of HCP immunization should include screening for evidence of immunity (Table 51-2) of existing staff as well as routine evaluation of incoming staff (see also Chapter 80). Some hospitals require evidence of immunity to some or all of these vaccine-preventable diseases, particularly measles, as a condition of employment.
All hospitals should have standard guidelines and procedures for identifying HCP with or exposed to infectious diseases and for managing situations in which personnel have been exposed or may be infectious. For situations involving measles, rubella, and mumps, these procedures are greatly simplified if the HCP already possess documented evidence of immunity, preferably through rapidly retrievable electronic records. Since the elimination of measles and rubella in the United States, the number of reported cases of these two diseases has declined substantially. Nevertheless, importations continue to occur, and the occurrence of even a single case in a hospital setting requires immediate reporting to the local or state health department and rapid response and control efforts in collaboration with local public health agencies.
Promptly instituting and complying with proper isolation precautions for patients with known or suspected communicable infections protects personnel and patients. In addition, hospital-acquired infections have been demonstrated to spread from patients and hospital personnel to their community contacts, as well as from the community to hospital settings. Transmission of infectious diseases is theoretically possible anywhere in hospitals where individuals, including HCP, patients, volunteers, trainees, and
visitors, may come into contact with those diseases. This includes waiting areas, cafeterias, playrooms, and other locations. Because visitors, friends, and relatives of hospital staff (including small children) may be infected or incubating infections, the important relationship between hospitals and their communities must be considered in developing prevention and control programs. Visitors, particularly children, may need to be screened for present or incubating infectious diseases before they are allowed to enter all or some patient care areas.
visitors, may come into contact with those diseases. This includes waiting areas, cafeterias, playrooms, and other locations. Because visitors, friends, and relatives of hospital staff (including small children) may be infected or incubating infections, the important relationship between hospitals and their communities must be considered in developing prevention and control programs. Visitors, particularly children, may need to be screened for present or incubating infectious diseases before they are allowed to enter all or some patient care areas.
TABLE 51-1 Measles, Mumps, Rubella and Parvovirus B19 (Erythema Infectiosum): Incubation, Infectious and Isolation Periods | |||||||||||||||||||||||||||
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MEASLES
Epidemiology
Prior to the licensure and availability of a live measles vaccine in 1963, approximately 95% of persons living in urban areas of the United States were infected with measles by the age of 15 years, and 3 to 4 million cases occurred annually (7,8). From 1950 to 1959, an average of 549,000 measles cases and 495 measles deaths were reported annually (9). After vaccine licensure, the incidence of measles declined rapidly with >99% reduction in the reported incidence in the United States by 1988 (10). This was associated with declines in measles-related hospitalizations and deaths.
In 1989, in response to outbreaks occurring in vaccinated school-aged children, two doses of measles, mumps, and rubella (MMR) vaccine were recommended for children (11,12). A major resurgence of measles occurred in the United States from 1989 to 1991 with 55,662 cases, 11,000 hospitalizations, and 124 deaths reported; the highest incidence was among preschoolers (<5 years) followed by adolescents (10-19 years)(13,33). Implementation of the two-dose MMR vaccine requirement and increased focus on improving vaccine coverage among preschoolaged children resulted in further declines in incidence with <140 measles cases reported annually between 1997 and 2001, an incidence of <1 measles case per million population (14). With this reduced incidence and lack of sustained endemic transmission, measles was declared “eliminated” from the United States in 2000 (1). During the postelimination era (2001-2008), 557 measles cases were reported in the United States (median: 56 cases, range: 37-140 cases per year) of which 232 (42%) cases were imported from 44 different countries, and the majority of the remaining cases were associated with these importations (15). As measles remains endemic in many other parts of the world, importations into the United States will continue to occur (3,15,16).
Once a disease primarily of childhood, measles may now affect persons of any age in the United States. Although the incidence of measles remains highest in the most susceptible age groups (infants <12 months and children aged 12-15 months, because they have not yet been vaccinated), the highest proportion of cases in the postelimination era has been among adults (40%), followed by preschool children (32%) (15). Measles epidemiology
is now mainly determined by the characteristics of the imported case and the people they come into contact with.
is now mainly determined by the characteristics of the imported case and the people they come into contact with.
TABLE 51-2 Measles, Mumps and Rubella: Presumptive Evidence of Immunity and Vaccination Requirements for Healthcare Personnel | |||||||||||||||||||||
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In addition, in recent years, there has been an increase in the number of measles outbreaks among populations who choose not to vaccinate because of personal beliefs. In the United States in 2008, 140 measles cases were reported—the highest number of cases annually since measles was declared eliminated (15). Of the nine outbreaks that year, six were related to personal-belief exemptors, and almost all these cases were children (15), including two children who were infected while visiting their mother in the hospital (5). In 2009, six of the eight outbreaks were associated with personal-belief exemptors (CDC, unpublished data). To maintain measles elimination in the United States, it will be necessary to sustain high MMR vaccine coverage among children and other groups at high risk of exposure and transmission, including HCP.
Measles in Medical Settings Prior to measles elimination in the United States, measles was commonly transmitted to and among patients in outpatient departments, in-patient wards, and emergency departments, and instances of measles transmission and outbreaks in medical settings in the United States and other countries have been well described (17, 18, 19 and 20). Visiting a hospital emergency room was identified as a risk factor for measles infection during community measles outbreaks in Houston and Los Angeles in 1989 (21). The predominant setting of transmission for 24 (20%) of the 120 measles outbreaks reported during 1993 to 2001 was healthcare facilities (22). Measles outbreaks have resulted in lost productivity and high containment costs for healthcare facilities (23, 24 and 25). In addition, medical facilities can contribute to the propagation and amplification of community measles outbreaks (21,26,27).
Because of the severity of measles, patients usually seek medical care, and as a result, HCP have a higher risk of being exposed to and acquiring measles. In a study of a measles outbreak in Clark County, Oregon, in 1996, HCP were 19 times more likely to be infected with measles than the general adult population of the county (23). Measles has been reported in persons of virtually all occupations providing patient or ancillary services including nurses, physicians, laboratory and radiology technicians, clerks, nursing assistants, and medical and nursing students (28). Transmission has been reported between patients, between HCP, from patient to HCP, and from HCP to patient. In many instances, the patient contact that led to measles in the HCP did not qualify as direct patient care, which illustrates the extreme transmissibility of measles virus. Visitors were rarely identified as the source for measles transmitted in these settings.
Almost 30% of HCP who acquired measles in medical settings from 1985 to 1991 were born before 1957 (i.e., they were older than the age for routine vaccination) (28). Studies among HCP indicated that up to 5% of HCP born before 1957 lacked measles antibodies (29,30). A recent study on measles seroprevalence among 469 newly
hired hospital HCP born before 1957 revealed that only 1.3% were measles seronegative (31).
hired hospital HCP born before 1957 revealed that only 1.3% were measles seronegative (31).
In 2008, a measles outbreak occurred in Arizona with 14 confirmed cases, including 7 healthcare-associatedacquired infections—the largest reported healthcare-associated measles outbreak in the United States since 1989 (5). Healthcare-associated transmission included patient-to-HCP, patient-to-patient, patient-to-visitor, and HCP-to-patient. During the screening of 7,195 HCP in two hospitals during this outbreak, 1,776 (25%) were found to lack evidence of measles immunity in their employee health record. Among the 1,583 of these HCP who underwent serologic testing for measles IgG antibodies, 18 of the 506 HCP (4%) born before 1957 and 121 of the 1,077 (11%) HCP born during or after 1957 were found to be seronegative. The two hospitals spent US$799,136 responding to and containing 7 cases in these facilities.
Between 2001 and 2008, 27 reported measles cases were transmitted in healthcare facilities, accounting for 5% of all reported US measles cases; 8 cases occurred among HCP, 6 (75%) of whom were unvaccinated or had unknown vaccine status (15).
Clinical Description
Measles is an acute viral infection that is characterized by a generalized maculopapular rash and high fever. Following an incubation period of 10 to 12 days (range: 7-18 days), the patient typically develops a prodrome consisting of fever and malaise, followed by cough, coryza, and conjunctivitis. The characteristic maculopapular rash usually appears 2 to 4 days after onset of the prodromal symptoms and first appears on the face, and then spreads to the trunk and extremities. The rash lasts 5 to 7 days and fades in order of appearance. An enanthem, characterized by small bluishwhite spots on a red background (Koplik’s spots), may be seen on the buccal mucosa from 2 days before to 2 days after onset of rash. A person with measles is considered to be infectious from 4 days before until 4 days after rash onset.
Measles may be associated with serious complications. The most common complications of measles are otitis media, diarrhea, and pneumonia. Pneumonia is the most common cause of death and may be caused by the measles virus or by a secondary bacterial or viral infection. Measles encephalitis is reported once in every 1,000 cases and can result in permanent neurologic sequelae or death. The age-specific complication rates are highest among infants, children between 1 and 4 years old, and adults over 20 years, and lowest in children 5 to 19 years old (32). Measles can be severe in immunocompromised patients, particularly in those with abnormalities of cellular immunity. From 2001 to 2008, 23% of reported measles cases in the United States required hospitalization (15). In the United States between 1987 and 2002, the case fatality rate for measles was 2 to 3 per 1,000 cases (33); two deaths due to measles occurred among the 557 reported cases between 2001 and 2008 (15). Another serious complication is subacute sclerosing panencephalitis (SSPE), which is a rare progressive neurologic disorder caused by a persistent infection of the brain with aberrant measles virus. The onset of behavioral and intellectual deterioration usually occurs 6 to 8 years after wild-type measles infection. SSPE is almost universally fatal (34).
Pathogenesis
The measles virus is a single-stranded RNA virus of the Paramyxovirus family. The measles virus can survive for at least 2 hours in fine droplets, and airborne spread in medical and other settings has been documented (35). Secondary attack rates of over 90% have been documented among susceptible populations (36,37). Neither a long-term infectious carrier state nor an animal reservoir is known to exist. Infection with measles virus is thought to confer lifelong immunity from clinical measles.
The primary site of measles infection is the respiratory epithelium of the nasopharynx. Generally, primary viremia with infection of the reticuloendothelial system occurs 2 to 3 days after invasion and replication in the respiratory epithelium. A second viremia occurs 5 to 7 days after initial infection, following further viral replication in regional and distal reticuloendothelial sites. During this viremia, there may be infection of the respiratory tract, skin, conjunctiva, and other organs. The characteristic pathologic feature of measles infection is the presence of multinucleated giant cells, which are found in the reticuloendothelial (Warthin-Finkeldey cells) or in the respiratory epithelium. In an immunocompetent person, measles virus is shed from the nasopharynx beginning with the prodrome until 4 days after rash onset. Immunocompromised persons with measles may shed the virus for a longer time.
Diagnosis
Since measles has become a rare disease in the United States, few younger clinicians have ever seen a patient with measles. The key to diagnosing measles is having a high index of suspicion in any patient with a generalized rash, fever and cough, coryza, or conjunctivitis and performing the appropriate laboratory tests. Recent international travel or exposure to persons with recent international travel should increase the diagnostic suspicion of measles. A history of vaccination, even with multiple doses of measles vaccine, does not preclude the diagnosis.
Laboratory testing is critical in confirming the diagnosis of measles. Measles may be confirmed by the presence of measles immunoglobulin M (IgM) antibodies in a single serum specimen, immunoglobulin G (IgG) seroconversion, a fourfold rise in IgG antibodies, isolation or detection of the measles virus by reverse transcriptase polymerase chain reaction (RT-PCR) (38). For IgM testing, enzyme immunoassay (EIA) is the most common assay currently in use and is commercially available. IgM antibodies appear with or soon after rash onset, peak 1 to 2 weeks later, and fall to nondetectable levels 1 to 2 months after the appearance of the rash. Serum specimens for IgM testing should be collected at the first clinical contact with a person with suspected measles. In previously vaccinated persons, the IgM response may be absent or short-lived, and additional testing, particularly viral testing, may be warranted (39).
The measles virus can be cultured from throat swabs, urine, nasal swabs, or whole blood. A throat or nasopharyngeal swab collected from first day of rash through 3 days following onset of rash is the preferred specimen for viral testing, although swabs collected up to 7 days after rash onset may still yield virus. Isolation of measles virus in culture or detection of measles virus by RT-PCR confirms
the diagnosis of measles (38). As most measles cases in the United States are currently associated with importations, the genotyping of viral specimens is of importance since this allows for a better understanding of the measles viruses being imported into or detected in the United States and the global epidemiology of the disease.
the diagnosis of measles (38). As most measles cases in the United States are currently associated with importations, the genotyping of viral specimens is of importance since this allows for a better understanding of the measles viruses being imported into or detected in the United States and the global epidemiology of the disease.
Prevention and Control
Because of the ease of transmission of measles, the fact that cases may present in medical facilities before onset of rash and recognition of measles as the diagnosis and because measles cases are frequently misdiagnosed, particularly during the prodrome, prevention of healthcare-associated measles transmission is challenging. However, a number of strategies will lower the risk. These include strategies to (a) maintain a high awareness among staff that a measles case could enter the facility, (b) assess the presumptive evidence of immunity of HCP, (c) maintain high vaccine coverage in the health facility staff, (d) promptly identify and isolate HCP and patients with febrile rash illness clinically compatible with measles, (e) identify and vaccinate potentially exposed patients, (f) exclude potentially infectious HCP from duty in the healthcare facility, (g) observe appropriate procedures for standard and airborne isolation in separate waiting areas, (h) inform health authorities promptly of suspected and confirmed measles cases, and (i) administer immune globulin as needed to selected immunocompromised patients and HCP where live viral vaccines, such as measles vaccine, are contraindicated (12,38,40,41,42).
Routine Vaccination Recommendations Live, attenuated measles vaccine is now available in the United States only as combined MMR vaccine. The Advisory Committee for Immunization Practices (ACIP) and Hospital Infection Control Practices Advisory Committee (HICPAC) recommend that all HCP should have documented immunity to measles. Vaccination with two doses of live, attenuated MMR vaccine is recommended for all HCP who lack evidence of immunity (see below) unless otherwise contraindicated (Table 51-2).
Presumptive Evidence of Immunity to Measles All HCP should have documented evidence of immunity to measles (Table 51-2). Adequate presumptive evidence of immunity to measles is defined as (a) documentation of administration of two doses of appropriately spaced live measles virus vaccine on or after the first birthday, (b) laboratory evidence of immunity, (c) laboratory confirmation of disease, or (d) birth before 1957 (43). Although most persons born in the United States before 1957 are likely to have been infected with measles naturally, ACIP and HICPAC suggest that healthcare facilities should consider vaccinating personnel without laboratory evidence of immunity or disease born before 1957 because of the potential for measles exposure in healthcare facilities and disruption that may result if an outbreak does occur. For HCP who have two documented doses of MMR vaccine or other acceptable evidence of immunity to measles, postvaccination serologic testing for immunity is not recommended. In the event that an HCP who has two documented doses of MMR vaccine is serologically tested and found to have negative or equivocal measles titer results, it is not recommended that the individual receive an additional dose of MMR vaccine. Documented age-appropriate vaccination is acceptable evidence of immunity irrespective of the results of subsequent serologic testing.
Management of Patients and Healthcare Personnel with Measles Patients with suspected or confirmed measles should be placed on Airborne Precautions for 4 days after the onset of rash (42). If airborne infection isolation rooms are not available, the patient should be placed in a room with the door closed and asked to wear a surgical mask (44). Only HCP with adequate presumptive evidence of immunity should provide care to a person with suspect or confirmed measles. Immunocompromised persons with measles (e.g., persons with acquired immunodeficiency syndrome) may shed virus for extended periods and should be kept on Airborne Precautions for the duration of their hospitalization for the acute illness.
If an HCP is suspected of having measles, they should be excluded from work until a diagnosis of measles can be ruled out. An HCP with confirmed measles should be excluded from duty for 4 days from the day of onset of rash.
Management of Measles Exposures and Outbreaks in Healthcare Settings If measles exposures occur in a healthcare facility, all contacts (those exposed during the infectious period) should be immediately evaluated for evidence of measles immunity.
Exposed HCP who cannot document evidence of measles immunity should be offered the first dose of MMR vaccine immediately and be excluded from work from the 5th through the 21st day following exposure (12). The second dose should be administered 28 days after the first. Those with documentation of one vaccine dose may remain at work and should receive the second dose. During an outbreak, HCP born before 1957 without laboratory confirmation of immunity or disease should receive two doses of the MMR vaccine; the first dose should be immediately followed by the second dose at least 28 days later. Serologic testing of HCP before vaccination is not recommended during an outbreak because arresting measles transmission requires rapid vaccination of HCP who lack evidence of measles immunity. The need to screen, wait for results, and then contact and vaccinate seronegative persons can impede the rapid vaccination needed to curb the outbreak. Serologic testing performed prior to vaccination may be used to guide the need for a second dose. HCP without evidence of measles immunity, for whom MMR vaccine is contraindicated, should receive immune globulin and should be excluded from work, and observations should continue for signs and symptoms of measles for 28 days after exposure, because immune globulin might prolong the incubation period.
Exposed patients without evidence of immunity should be offered the first dose of MMR vaccine or measles immune globulin (if vaccine is contraindicated) and should be discharged from hospital, if feasible. If they remain in the hospital, they should be quarantined from the 5th through the 21st day following exposure and should receive their second MMR vaccine 28 days after the first dose. If they have received immune globulin, they should be excluded for 28 days.
Other contacts (e.g., visitors, persons exposed in emergency rooms) should be identified, and information about them should be provided to local and state health departments so that these contacts can be followed up for evidence of measles immunity, need for vaccination or immune globulin, and for development of signs and symptoms of measles.
Any hospital contact who develops measles-compatible symptoms should be evaluated, isolated/excluded from work (as appropriate), and appropriate infection-control measures should be implemented to prevent further spread.
MUMPS
Epidemiology
Prior to the availability of mumps vaccine, epidemics of mumps occurred in the United States approximately every 3 years with peak incidence during the winter and spring (45). The infection largely occurred among children aged 5 to 9 years; by age 14, approximately 90% of children living in urban areas had already been infected with mumps (46). The epidemiology of the disease significantly changed following the licensure of a mumps vaccine in 1967. After that, reported cases of mumps in the United States began to decline steadily from 152,209 cases reported in 1968 to 2,982 cases reported in 1985 (47,48). Between 1986 and 1991, the United States experienced a resurgence of mumps, particularly among 10- to 14-year-olds and 15- to 19-year-olds, caused initially by a failure to vaccinate older cohorts of children and later characterized by one-dose vaccine failures (49,50). The recommendation for a routine two-dose schedule for MMR to improve measles control in 1989 likely contributed to further declines in the incidence of mumps throughout the 1990s, and in 2003, a record low of 231 cases was reported nationally (48); this number represented a >99% decline from the 152,209 cases reported in 1968—the year after the live mumps vaccine was licensed.
During 2006, the United States experienced a large mumps outbreak with 6,584 cases—the largest number of cases reported since 1987 (51). The outbreak primarily affected college students from the Midwest, many of whom had already received two doses of the MMR vaccine. Mumps incidence again declined after this outbreak with 800 cases of mumps reported in 2007 and 454 cases reported in 2008 (52,53). Again in 2009 to 2010, a large outbreak of mumps occurred in orthodox Jewish communities, primarily in the northeastern United States. The majority of cases (61%) occurred among persons aged 7 to 18 years; 75% of cases, where vaccine status was known, had previously received two doses of MMR vaccine (54). In 2006 and 2009-2010 outbreaks, crowded social, religious, educational, or living environments appeared to be fueling the transmission of mumps. Although the effectiveness of the mumps component of the MMR vaccine is lower than that of the measles and rubella components, it appears sufficient to maintain mumps control and prevent outbreaks in most community settings. Estimates of the effectiveness of the mumps vaccine using the Jeryl Lynn or derived strains have varied in previous studies, ranging from 62% to 91% after one dose and from 79% to 95% after two doses (55, 56 and 57,58).
Although most cases of mumps in HCP may be community acquired, sporadic transmission of mumps within hospitals to patients and staff is well documented (6). Cases of mumps in HCP and patients have been reported following healthcare-associated exposure, particularly in longterm care facilities housing adolescents and young adults. Outbreaks of mumps within hospitals, however, have only rarely been reported (59,60). Presumably, the rare occurrence of healthcare-associated mumps outbreaks is because mumps virus is less communicable than measles and many other viruses, and mumps results in hospitalization less commonly. The level of mumps transmission in the surrounding community may also affect the risk for introduction into hospitals (6). During the 2006 mumps outbreak, a single healthcare institution experienced ongoing transmission of mumps for 1 month, affecting seven employees and two inpatients (60).
Clinical Description
Mumps is an acute viral illness, classically characterized by the presence of unilateral or bilateral parotitis. Onset of the disease usually occurs with nonspecific prodromal symptoms such as anorexia, myalgia, malaise, headache, and low-grade fever lasting up to several days. Parotitis, the predominant clinical feature, usually develops an average of 16 to 18 days (range: 12-25 days) after exposure. However, mumps infection may present only with nonspecific, primarily respiratory, symptoms or may be a subclinical infection (56). Parotitis may be accompanied by earache and pain on chewing and may involve other salivary glands, including the submaxillary and sublingual glands. Parotitis is usually accompanied by moderate fever, but temperature may range from normal up to 40°C (104°F). Symptoms tend to decrease after 1 week and are usually gone by 2 weeks.
Complications of mumps include orchitis, affecting up to 37% of postpubertal males (61), and mastitis, affecting up to 31% of females older than 15 years (62). Oophoritis occurs in 5% of postpubertal females. Sterility or long-term infertility is thought to be a rare sequelae associated with orchitis and oophoritis. Meningeal signs may appear in up to 15% of cases, and pancreatitis, usually mild, may be present in up to 4% of cases (63). An association between maternal mumps infection during the first trimester of pregnancy and an increase in the rate of spontaneous abortion or intrauterine fetal death has been reported in some studies but not in others (64,65).
Serious complications of mumps are rare. Encephalitis occurs in <0.3% of apparent mumps infections (66,67). Permanent sequelae are rare, but the reported encephalitis case fatality rate has averaged 1.4% (67a). Transient highfrequency deafness may occur in up to 4% of mumps cases (63). Permanent deafness may occur at a rate of 1 case per 15,000 to 20,000 cases of mumps.
Pathogenesis
The mumps virus is single-stranded RNA virus in the Paramyxovirus family. The mumps virus is transmitted in saliva and respiratory secretions (63,68). Mumps is acquired through the nose or mouth by direct contact with infected
droplets, saliva, or contaminated fomites but appears to be less efficiently transmitted than some other infectious diseases such as measles and chickenpox; the secondary clinical attack rate in susceptible household contacts <15 years was estimated to be 31%, 61%, and 76% for mumps, chickenpox, and measles respectively (69). Primary viral replication occurs in the epithelium of the respiratory tract and possibly in regional lymph nodes. This is followed by viremia, which persists for 3 to 5 days, disseminates mumps virus throughout the body with localization in glandular tissue, and terminates with the development of humoral antibody (70). Mumps virus has been isolated in saliva from 7 days before parotitis to 8 days after onset of disease; cessation of viral shedding coincides with the appearance of virus-specific secretory immunoglobulin A (63,68,71,72,73). However, viral shedding and therefore transmission risk are highest 1 to 2 days prior to and following parotitis onset, and most transmission likely occurs before and within 5 days of parotitis onset. During viremia, virus may be disseminated to the salivary glands, meninges, kidneys, testes, and other organs. Viruria is frequent and may last 10 days or more. Virus can be isolated from breast milk of infected women (74). Parotitis accounts for most of the observed elevation of serum and urine amylase. Development of measurable neutralizing antibodies appears to correlate best with immunity to mumps.
droplets, saliva, or contaminated fomites but appears to be less efficiently transmitted than some other infectious diseases such as measles and chickenpox; the secondary clinical attack rate in susceptible household contacts <15 years was estimated to be 31%, 61%, and 76% for mumps, chickenpox, and measles respectively (69). Primary viral replication occurs in the epithelium of the respiratory tract and possibly in regional lymph nodes. This is followed by viremia, which persists for 3 to 5 days, disseminates mumps virus throughout the body with localization in glandular tissue, and terminates with the development of humoral antibody (70). Mumps virus has been isolated in saliva from 7 days before parotitis to 8 days after onset of disease; cessation of viral shedding coincides with the appearance of virus-specific secretory immunoglobulin A (63,68,71,72,73). However, viral shedding and therefore transmission risk are highest 1 to 2 days prior to and following parotitis onset, and most transmission likely occurs before and within 5 days of parotitis onset. During viremia, virus may be disseminated to the salivary glands, meninges, kidneys, testes, and other organs. Viruria is frequent and may last 10 days or more. Virus can be isolated from breast milk of infected women (74). Parotitis accounts for most of the observed elevation of serum and urine amylase. Development of measurable neutralizing antibodies appears to correlate best with immunity to mumps.
Diagnosis
When parotitis is present, the clinical diagnosis of mumps is generally apparent. Although parotitis may be caused by other agents such as parainfluenza and coxsackievirus, bacterial infections, systemic diseases such as lupus and sarcoid, and certain drugs, mumps virus is the only known cause of epidemic parotitis. Because mumps is now a rare disease in the United States, diagnostic testing for persons with parotitis with no other apparent cause is recommended (75). Laboratory diagnosis of mumps requires either detection of mumps IgM antibodies, a significant rise in serum IgG antibody titers between acute and convalescent phase sera, IgG seroconversion from negative to positive, isolation of mumps virus, or detection of virus by RT-PCR (76).
Laboratory diagnosis of mumps in highly vaccinated populations may be challenging, and the timing of specimen collection and the utility of testing depend on the vaccination history of the person suspected of having mumps. In general, sera for IgM testing or as the acute specimen for examining seroconversion should be collected as soon as possible after onset of parotitis. In unvaccinated persons, IgM antibody is detectable within 5 days of onset of symptoms, peaks in about 1 week, and remains elevated for up to several months; for persons who have been previously vaccinated, the IgM response may be absent, and a negative result should not be used to rule out the diagnosis of infection. The IgM-capture EIA is the most sensitive method for detecting antibodies but has limited commercial availability. Other IgM test methods are more variable in their sensitivity and specificity.
The convalescent specimen for IgG detection should be collected approximately 2 to 3 weeks after the acute specimen. In unvaccinated individuals, mumps IgG antibody rises early after the onset of symptoms and is long-lasting. Previously vaccinated individuals may already have high levels of IgG present at the time that the acute specimen is collected. Oral or buccal swab samples should be collected as soon as mumps disease is suspected. Samples collected when the patient first presents with symptoms, usually within 3 days of parotitis, have the best chance of having a positive result by RT-PCR.
Prevention and Control
Because viral shedding occurs before clinical symptoms begin and because mumps may occur as a nonspecific respiratory illness or as an asymptomatic infection, effective methods to reduce mumps transmission can be challenging. Preventing mumps through an effective vaccination program is the best approach to controlling this disease. Strategies for mumps prevention and control should be applied in all healthcare settings and include (a) assessing the presumptive evidence of immunity of HCP, (b) vaccination of those without evidence of immunity, (c) exclusion of HCP with mumps as well as those lacking presumptive evidence of immunity who are exposed to persons with mumps, (d) isolation of patients in whom mumps is suspected, and (e) implementation of Standard and Droplet Precautions.
Routine Vaccination Recommendations Live, attenuated mumps vaccine is now available in the United States only as combined MMR vaccine. The ACIP and HICPAC recommend that all HCP should have documented immunity to mumps. Since 2006 (77), vaccination with two doses of MMR vaccine has been recommended for all HCP who lack evidence of immunity (see below) unless otherwise contraindicated (Table 51-2).
Presumptive Evidence of Immunity to Mumps All HCP should have documented evidence of immunity to mumps (Table 51-2). Acceptable presumptive evidence of immunity to mumps is defined as (a) documentation of administration of two appropriately spaced doses of live mumps-containing vaccine on or after the first birthday, (b) laboratory evidence of immunity, (c) laboratory confirmation of disease, or (d) birth before 1957 (43). Most persons born before 1957 are likely to have been infected naturally and generally may be considered to be immune even if they may not have had clinically recognizable mumps. However, a recent serosurvey conducted in 488 HCP born before 1957 showed that 3.7% of persons tested did not have serologic evidence of mumps antibody (31). ACIP and HICPAC suggest that healthcare facilities should consider vaccinating personnel without laboratory evidence of immunity or disease born before 1957 because of the potential for mumps exposure in healthcare facilities and disruption that may result if an outbreak does occur.
Management of Patients and Healthcare Personnel with Mumps To prevent transmission, Standard and Droplet Precautions are recommended for patients with mumps, including a private room and use of masks for those providing care to the patient (42). These precautions should be maintained for 5 days after onset of parotitis. HCP with mumps should be excluded from work for 5 days after onset of parotitis (71).
Management of Mumps Exposures and Outbreaks in Healthcare Settings If mumps exposure occurs in a healthcare facility, all contacts (those exposed during the infectious period) should be evaluated for evidence of mumps immunity.
Exposed HCP without evidence of mumps immunity who are exposed to a person with mumps should be offered the first dose of MMR vaccine and should be excluded from duty from the 12th day after the first unprotected exposure through the 25th day after the last exposure. They should receive the second dose 28 days after the first dose. HCP with documentation of one vaccine dose may remain at work and should receive the second dose. During an outbreak of mumps, unvaccinated personnel born before 1957 who lack laboratory evidence of mumps immunity or laboratory evidence of disease should be vaccinated with two doses of MMR vaccine, 28 days apart. Serologic testing of HCP before vaccination is not recommended during an outbreak. The need to screen, wait for results, and then contact and vaccinate seronegative persons can impede the rapid vaccination needed to curb the outbreak. Serologic testing performed prior to vaccination may be used to guide the need for a second dose.
Exposed patients without evidence of immunity should be offered the first dose of MMR vaccine and should be discharged from the hospital, if feasible. If they remain in the hospital, they should be quarantined from the 12th day after the first unprotected exposure through the 25th day after the last exposure.
Other contacts (e.g., visitors, persons exposed in the emergency rooms) should be identified, and information about them should be provided to local and state health departments so that these contacts can be followed up for evidence of mumps immunity, the need for vaccination, and development of signs and symptoms of mumps.
Any hospital contact that develops mumps-compatible symptoms should be evaluated, isolated/excluded from work (as appropriate), and appropriate infection-control measures should be implemented to prevent further transmission.
RUBELLA
Epidemiology
During the global rubella pandemic that occurred between 1962 and 1965, an estimated 12.5 million cases of rubella occurred in the United States, resulting in considerable morbidity and mortality, including 11,250 therapeutic or spontaneous abortions, 2,100 neonatal deaths, and 20,000 infants born with congenital rubella syndrome (CRS) (78,79). The licensure of rubella vaccine in the United States in 1969 (80), and its use, primarily in children, led to dramatic declines in the number of reported rubella cases in the United States from 57,686 cases in 1969 to 12,491 cases in 1976 (81). CRS cases also decreased dramatically from 68 in 1970 to 23 in 1976 (82). A resurgence of rubella from 1977 to 1978, primarily among older adolescents and young adults (12,83), led to a modification of the rubella vaccination strategy to target additional groups for vaccination including susceptible postpubertal girls and women, military recruits, college students, and persons in certain work settings (e.g., healthcare) (83, 84, 85 and 86). These recommendations resulted in a decrease in rubella cases in these age groups in the 1980s. During the mid 1990s to 2000, the majority of cases in rubella outbreaks were among foreign-born Hispanic adults from countries without a history of routine rubella vaccination programs (87, 88 and 89). Between 2000 and 2004, the median number of rubella cases reported annually was 18 (range: 7-176 cases) (90). In 2004, rubella was declared eliminated from the United States on the basis of data showing that the virus was no longer circulating endemically within the country’s borders (2).
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