Chapter 7: Measles

Disease Description

Measles is an acute viral illness caused by a single-stranded RNA virus in the family paramyxovirus, genus Morbillivirus. Measles is characterized by a prodrome of fever (as high as 105°F) and malaise, cough, coryza, and conjunctivitis, followed by a maculopapular rash.1 The rash starts typically on the face or at the hairline, subsequently spreading to the trunk to lower extremities. Measles is usually a mild or moderately severe illness. However, measles can result in complications such as diarrhea, dehydration, pneumonia, encephalitis, and death, with 20% of cases requiring hospitalization in the United States. Approximately one case of encephalitis and two to three deaths may occur for every 1,000 reported measles cases.23

One rare long-term sequela of measles virus infection is subacute sclerosing panencephalitis (SSPE), a fatal disease of the central nervous system that generally develops 7–10 years after infection. Among persons who contracted measles during the resurgence in the United States (U.S.) in 1989–1991, the risk of SSPE was estimated to be 7–11 cases/100,000 cases of measles.4 The risk of developing SSPE may be higher when measles occurs prior to the second year of life.4

The average incubation period for measles is 11–12 days, and the average interval between exposure and rash onset is 14 days, with a range of 7–21 days.15Persons without immunocompromising conditions with measles are considered infectious from four days before until four days after onset of rash, with the rash onset being considered as day zero (for additional information, see "Isolation of Cases" section below).6

Background

Epidemiology of measles in the United States

Measles cases in the pre-elimination era

In the decade prior to the licensure of live measles vaccine in 1963, an average of 549,000 measles cases and 495 measles deaths were reported annually.7 However, almost every American was affected by measles during their lifetime, and it is estimated that 3–4 million measles cases occurred each year.89 Following implementation of a one dose measles vaccine program in the 1960s, there was a rapid and significant reduction in the reported incidence of measles in the United States through the 1980s, resulting in declines in measles-related hospitalizations and deaths.1011 By the late 1980s, however, measles outbreaks were still occurring among school-aged children who had received a single dose of measles vaccine. In 1989, a second-dose vaccination schedule was recommended by the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP).11

During 1989–1991, a resurgence of measles occurred when over 55,000 cases and 123 deaths were reported. The epidemiology during the resurgence was characterized mainly by cases in preschool-aged children living in poor urban areas who had not been vaccinated on time with one dose of measles vaccine.12 Following the resurgence, a commitment of resources for improved implementation of the timely administration of the first dose of the vaccine, and increased implementation of two doses among school-aged children, led to further declines in measles cases.

In 2000, endemic measles was declared "eliminated" from the United States.13 For measles, elimination is defined as the absence of endemic measles transmission for a period of 12 months or more in the presence of an adequate surveillance system.14

Measles cases in the post-elimination era

During 2001–2019, 3,873 measles cases were reported in the United States.15 The median number of measles cases reported per year was 86 (range: 37–1,274 cases/year). Most (87%) U.S. resident case-patients were unvaccinated (70%) or had unknown vaccination status (17%). Of the 3,873 reported measles cases, 747 (19%) were importations, 2,275 (59%) were epidemiologically linked to these importations, and 693 (18%) either had virologic evidence of importation or had been epi-linked to cases with virologic evidence of importation. There were a median of 28 importations per year during this timeframe. Only 158 (4%) cases had an unknown source. Unknown source cases represent cases where epidemiologic or virologic linkage to an imported case was not detected. During 2001–2019, the majority of importations were the result of unvaccinated U.S. residents who had traveled internationally; most importations resulted from travel to countries in the WHO European and Western Pacific Regions.16

During 2020–2023, 241 measles cases were reported in the United States. The median number of measles cases reported per year was 53 (range: 13–121 cases/year). Most U.S. resident case-patients were unvaccinated (89%) or had unknown vaccination status (5%). Of the 241 reported measles cases, 74 (31%) were importations, 52 (22%) were epidemiologically linked to these importations, and 106 (44%) either had virologic evidence of importation or had been epi-linked to cases with virologic evidence of importation. There were a median of 22 importations/year. Only 7 (3%) cases had an unknown source. During 2020–2023, the majority of importations were the result of unvaccinated U.S. residents who had traveled internationally; most importations resulted from travel to countries in the World Health Organization (WHO) African, European, and Western Pacific Regions.

Although measles elimination has been achieved in the United States, importation of measles will continue to occur as measles remains endemic in many other parts of the world.

Measles outbreaks in the post-elimination era

Outbreaks* of measles in the United States in the post-elimination era mostly involve persons who are unvaccinated or have an unknown vaccination status. Thus, current measles epidemiology in the United States is largely determined by characteristics of the imported cases and their susceptible contacts, and fine-scale pockets of under-vaccination rendering certain communities at risk. Two-dose MMR coverage of 95% or higher is generally considered the threshold required to suppress community transmission and to prevent outbreaks.

The settings of measles transmission in prior outbreaks have included households, educational institutions (e.g., schools, daycares), churches, healthcare facilities, homeless shelters, or other congregate settings. Lack of adherence to existing recommendations for measles prevention among groups at high risk (e.g., unvaccinated individuals traveling internationally) can spread measles to susceptible populations, including infants too young to be vaccinated or persons for whom vaccination is contraindicated (e.g., immunocompromised persons).

Historically, because of high population immunity and high measles vaccine effectiveness, the size of measles outbreaks in the United States has been limited during the post-elimination era. During 2001–2019, 158 outbreaks of measles occurred, with a median case count of 5 (range: 3–697 cases). Large outbreaks in the United States within close-knit, undervaccinated communities highlighted the importance of maintaining high levels of measles immunity across the population through routine measles vaccine coverage.171819 Measles elimination status was threatened by the largest of these outbreaks in New York City and New York State, which stretched for approximately ten months during 2018–2019.1517

Two large outbreaks occurred during 2020–2023. During 2021, multiple small outbreaks occurred among Afghan evacuees being resettled to the United States as part of Operation Allies Welcome; a total of 47 cases of measles were diagnosed at six separate resettlement locations but no spread to the surrounding community occurred.20 During 2022, 85 cases were diagnosed in Central Ohio, with transmission occurring primarily among undervaccinated children in healthcare facilities, childcare facilities, and households.21

Responding to measles cases and outbreaks is time consuming and costly for local and state health departments.2223 The overall costs to health departments to contain 16 outbreaks during 2011 amounted to an estimated $2.7 million to $5.3 million U.S. dollars. The economic burden of controlling measles spread in health care settings amounts to an estimated $19,000 to $114,286 U.S. dollars per case.

* National reporting: An outbreak is defined as a chain of transmission including 3 or more cases linked in time and space.

Global measles

Despite tremendous achievements towards global measles mortality reduction and elimination goals, and an estimated 57 million measles deaths prevented by vaccination from 2000–2022, there have been setbacks and challenges to global elimination.24 In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP) with the goal of achieving measles elimination in at least five WHO regions by 2020.14 However, by the end of 2020, none of the six WHO regions had achieved and sustained elimination.

Global MCV1 coverage increased from 72 to 84% between 2000–2010, and measles cases decreased from 853,479 in 2000 to 343,806 in 2010.25 However, global MCV1 coverage plateaued at 84-86% from 2010 through 2019 and dropped to 81–83% during 2020–2022.24 Among the 194 WHO countries, 65 (34%) achieved ≥95% MCV1 coverage in 2022; the 21.9 million infants who did not received MCV1 through routine immunization services during 2022 represented a decrease of 2.5 million (10%) compared with 2021. Global coverage of MCV2 increased from 17% during 2000 to 71% during 2019 but has subsequently plateaued at 71–74% during 2022.24

Recent global epidemiology of measles has been summarized by Minta and colleagues in a 2023 publication.24 During 2000–2016, measles incidence fell 88% from 145 cases to 18 cases per 1 million population; however, there was a surge in global measles incidence during 2016–2019; 837,922 measles cases were reported during 2019, representing an incidence of 120 cases per 1 million population. Measles incidence subsequently declined during 2020–2021, with an incidence of 17 cases per 1 million population reported during 2021. The observed measles incidence decrease may reflect actual changes related to increased immunity after the 2017–2019 global resurgence of measles, reduced viral transmission associated with the mitigation measures implemented during the COVID-19 pandemic, surveillance system underperformance, or a combination of factors. During 2022, reported measles cases increased 67%, from 123,171 cases during 2021 to 205,153 during 2022. Modeling of total cases and deaths estimated that 9,232,300 measles cases occurred during 2022, with an estimated 136,200 deaths (i.e., approximately 373 deaths/day). During 2022, large measles outbreaks were reported in several countries in the African, European, and Eastern Mediterranean, and South-East Asia regions.

In the Americas, under the leadership of the Pan American Health Organization (PAHO), Ministries of Health implemented an aggressive measles elimination program in 1994. By 2002, scientific evidence suggested that endemic transmission of measles virus in the Americas was interrupted for ≥12 months.26 However, imported cases from endemic areas of the world continued to occur, resulting in sizable outbreaks in several countries, including Ecuador, Canada, and the United States. In September 2016, after over two decades of commitments and efforts by Member States to control measles, the Region of the Americas was the first in the world to verify the elimination of measles.27 However, increased importation of measles led to outbreaks in Venezuela and Brazil that led to loss of national elimination in 2016 and 2018, respectively, due to prolonged endemic transmission lasting >12 months.28 As of 2022, Venezuela had subsequently re-verified elimination of measles with PAHO, while Brazil remained classified as having ongoing endemic measles transmission.29

WHO remains committed to achieving and sustaining measles elimination globally, per the Immunization Agenda 2030.30 Achieving elimination in other regions of the world will have direct benefits in the United States.

Maintenance of Elimination

The declaration of endemic measles elimination in the United States was made in 2000.913 The key strategies for maintaining the elimination of measles in the United States are:

• Vaccinating children at age 12–15 months with a first dose of measles, mumps, rubella (MMR) vaccine;
• Ensuring that school-age children receive a second dose of MMR vaccine;
• Vaccinating high-risk groups, such as health care personnel and international travelers including infants 6 to 11 months of age;
• Maintaining measles awareness among health care personnel and the public; and
• Working with U.S. government agencies and international agencies, including the WHO, on global measles mortality reduction and elimination goals.

In addition, pockets of unvaccinated populations can pose a risk to maintaining elimination.1531 Thus, rapid detection of cases is necessary so that appropriate control measures can be quickly implemented. This is to prevent imported strains of measles virus from establishing endemic chains of transmission. Outbreak preparedness and response remains one of the five core strategies in the 2021–2030 WHO strategic plan for global measles and rubella.32

Vaccination

Live attenuated measles virus vaccine is incorporated into combination MMR vaccine and combination measles, mumps, rubella, and varicella (MMRV) vaccine. Monovalent measles vaccine is not available in the United States. For specific information about available MMR and MMRV vaccines, please refer to the Pink Book, which provides general recommendations, including vaccine schedule and use, vaccine contents, adverse events, vaccine storage and handling, and contraindications and precautions.

For prevention of measles, two doses of MMR vaccine are recommended routinely for children, with the first dose at age 12 through 15 months and the second dose at ages four through six years (school entry).33 ACIP recommends that separate MMR and varicella vaccines be given for the first dose in children aged 12–47 months; however, MMRV can be used if parents or caregivers express a preference.

Adults who do not have presumptive evidence of immunity (see "Presumptive Evidence of Immunity" below) should get at least one dose of MMR vaccine. Two doses of MMR vaccine are recommended for adults at high risk for measles, including international travelers, students at post-high school education institutions, and healthcare personnel.33

Vaccination recommendations for an outbreak setting are discussed in the "Control Measures" section in this chapter.

For more details on health care personnel please see the section "Health care settings" in this chapter.

Travel recommendations

Children 6–11 months of age who travel internationally should receive one dose of MMR vaccine optimally at least two weeks prior to travel. Because serologic response to the measles component of the vaccine varies among infants 6–11 months of age, children vaccinated before age 12 months should receive two additional doses of MMR or MMRV vaccine according to the routine recommended schedule.33

Children ≥12 months of age and adults who plan to travel outside the United States should receive a total of two doses of MMR vaccine, separated by at least 28 days. For children >12 months of age who have received a single MMR dose and have not yet reached the age of the routine 2^nd dose (i.e., 4–6 years), a 2^nd dose should be provided prior to international travel. Vaccination should be received ideally at least two weeks before travel to provide adequate protection; if this is not possible, vaccination can be received closer to travel dates.34

For additional information regarding measles prevention and response for international travelers, please see the Yellow Book.

Presumptive Evidence of Immunity

Acceptable presumptive evidence of measles immunity includes at least one of the following33:

• Written documentation of adequate vaccination—receipt of one or more doses of a measles-containing vaccine administered on or after the first birthday for preschool-age children and adults not at high risk, and two doses of measles-containing vaccine for school-age children and adults at high risk for exposure transmission (i.e., health care personnel, international travelers, and students at post-high school educational institutions); or
• Laboratory evidence of immunity; or
• Birth before 1957; or
• Laboratory confirmation of disease.

Persons who do not meet the above criteria are considered susceptible and should be vaccinated unless contraindicated.

For health care settings please see the section "Health care settings" below as the criteria are different.

Case Definition

The following case definition for case classification of measles cases, including case classifications for importation status, has been approved by the Council of State and Territorial Epidemiologists (CSTE) and was published in 2012.35

For additional information from CSTE on the case definition, including criteria for reporting, please see Public Health Reporting and National Notification for Measles.

Case definition for case classification

Clinical description:

• An acute illness characterized by:
  • Generalized, maculopapular rash lasting ≥3 days; and
  • Temperature ≥101°F or 38.3°C; and
  • Cough, coryza, or conjunctivitis

Probable:

• In the absence of a more likely diagnosis, an illness that meets the clinical description with:
  • No epidemiologic linkage to a laboratory-confirmed measles case; and
  • Noncontributory or no measles laboratory testing.

Confirmed:

• An acute febrile rash illness^† with:
  • Isolation of measles virus^‡ from a clinical specimen; or
  • Detection of measles virus-specific nucleic acid^‡ from a clinical specimen using polymerase chain reaction; or
  • IgG seroconversion^‡ or a significant rise in measles immunoglobulin G antibody^‡ using any evaluated and validated method; or
  • A positive serologic test for measles immunoglobulin M antibody^‡§; or
  • Direct epidemiologic linkage to a case confirmed by one of the methods above.

^† Temperature does not need to reach ≥101°F/38.3°C and rash does not need to last ≥3 days.

^‡ Not explained by MMR vaccination during the previous 6–45 days.

^§ Not otherwise ruled out by other confirmatory testing or more specific measles testing in a public health laboratory.

Note: Genotype identification by a WHO reference laboratory (CDC or a public health laboratory that has validated their measles virus sequence analysis) is required to distinguish wild type from vaccine strain if vaccinated within 21 days of rash onset.

Epidemiologic classification of internationally imported and U.S.-acquired

International importation: An internationally imported case is defined as a case in which measles results from exposure to measles virus outside the United States as evidenced by at least some of the exposure period (7–21 days before rash onset) occurring outside the United States and rash onset occurring within 21 days of entering the United States and there is no known exposure to measles in the United States during that time.

All other cases are considered U.S.-acquired.

U.S.-acquired case: An U.S.-acquired case is defined as a case in which the patient had not been outside the United States during the 21 days before rash onset or was known to have been exposed to measles within the United States.

U.S.-acquired cases are sub-classified into four mutually exclusive groups:

Import-linked case: Any case in a chain of transmission that is epidemiologically linked to an internationally imported case.

Imported-virus case: A case for which an epidemiologic link to an internationally imported case was not identified, but for which viral genetic evidence indicates an imported measles genotype, i.e., a genotype that is not occurring within the United States in a pattern indicative of endemic transmission.

An endemic genotype is the genotype of any measles virus that occurs in an endemic chain of transmission (i.e., lasting ≥12 months). Any genotype that is found repeatedly in U.S.-acquired cases should be thoroughly investigated as a potential endemic genotype, especially if the cases are closely related in time or location.

Endemic case: A case for which epidemiological or virological evidence indicates an endemic chain of transmission. Endemic transmission is defined as a chain of measles virus transmission that is continuous for ≥12 months within the United States.

Unknown source case: A case for which an epidemiological or virological link to importation or to endemic transmission within the United States cannot be established after a thorough investigation. These cases must be carefully assessed epidemiologically to assure that they do not represent a sustained U.S.-acquired chain of transmission or an endemic chain of transmission within the United States.

Note: Internationally imported, import-linked, and imported-virus cases are considered collectively to be import-associated cases.

States may also choose to classify cases as "out-of-state-imported" when imported from another state within the United States. For national reporting, however, cases will be classified as either internationally imported or U.S.-acquired. The possibility that a patient was exposed within his or her state of residence should be excluded; therefore, the patient either must have been out of state continuously for the entire period of possible exposure (at least 7–21 days before onset of rash) or have had one of the following types of exposure while out of state: a) face-to-face contact with a person who had probable or confirmed measles, or b) attendance in the same institution as a person with probable or confirmed measles (e.g., in a school, classroom, or childcare center).

Laboratory Testing

General Testing Information

Laboratory confirmation of measles infection is essential for all measles outbreaks and sporadic measles cases. Detection of measles-specific IgM antibody and measles RNA by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) are the most common methods for confirmation of measles infection. Testing for all suspect measles cases should ideally include both serologic testing and rRT-PCR to optimize sensitivity and specificity of testing.

To maximize the specificity of laboratory testing, it is important to restrict case investigation and laboratory testing to patients most likely to have measles (i.e., those who meet the clinical case definition or those who have risk factors for measles, such as being unvaccinated or reporting recent history of international travel). The threshold to test for measles may be lower during measles outbreaks when measles transmission is known to be occurring within a community or geographic area.

State health departments can provide guidance regarding available laboratory services and appropriate routing of specimens. Staff at the CDC Measles Laboratory are available for consultation and can assist with confirmatory testing as needed for measles. CDC has additional information on specimen collection and shipping for specimens referred to CDC.

During a measles investigation when community awareness is increased, many cases of febrile rash illness may be reported as suspected measles, and case counts may be inflated if these cases are included in the absence of laboratory confirmation. This is particularly important as the investigation is ending; at that point, laboratory confirmation should be sought for all suspected cases. Occasionally, suspected cases may include recently vaccinated individuals, especially if vaccination clinics were offered to contain outbreaks. For these cases, laboratory confirmation and case classification may be challenging without advanced diagnostic testing (see MeVA below).

For additional details about laboratory testing, see Chapter 22, Section F.

Serologic Testing

Serologic testing is recommended along with testing for viral nucleic acid (i.e., rRT-PCR) for suspect measles cases. There is no single serologic laboratory test capable of confirming with 100% confidence every true case of measles. Public health laboratories that use commercial measles assays are encouraged to fully characterize and validate the assays in their laboratories using test panels of true positive and negative specimens. Information regarding the performance characteristics of many of the commercially available enzyme immunoassay (EIA) kits is available by contacting the CDC Measles Laboratory.

For additional information about interpretation of measles serologic testing, see Chapter 22, Table 5.

IgM

Following measles virus infection in an unvaccinated individual, measles IgM antibodies appear within the first few days (1–4 days) of rash onset and peak within the first week after rash onset. IgM testing is most sensitive ≥3 days after rash onset, and IgM may not be detectable within the first three days. Detection of IgM may be variable in persons with pre-existing immunity who develop measles (see below). IgM can be detected for 6–8 weeks following an acute measles infection.

Because measles is a rare disease in the United States, even with the excellent laboratory tests available, false positive results for measles IgM will occur. To minimize the occurrence of false positive laboratory results, it is important to restrict case investigation and laboratory testing to patients most likely to have measles (i.e., those who meet the clinical case definition or those who have risk factors for measles, such as being unvaccinated or reporting recent history of international travel). Even so, testing for measles-specific IgM from persons with rash and fever can still produce false positive IgM results, as cross-reactivity with other causes of viral exanthem, such as parvovirus B19 or human herpesvirus 6, is known to occur.3637

The reference laboratory at CDC uses an IgM assay developed at CDC for measles serologic testing. The assay is an IgM capture EIA that utilizes a recombinant measles nucleoprotein (NP) antigen and has high sensitivity and specificity compared indirect EIAs.

IgG

Testing for evidence of immunity to measles can be performed by testing for measles-specific IgG. Testing for evidence of immunity should not include IgM, as any positive IgM result would be expected to be false positive in the absence of clinical concern for measles. Detection of IgG at the time of rash onset, or any time prior to symptom onset after exposure to measles, represents pre-existing immunity to measles, either through prior vaccination or prior measles infection.38 People with pre-existing immunity may develop an anamnestic response after exposure to wild-type measles, such that the IgG titer may rise in response to the exposure as early as six days after exposure.3940 However, regardless of the time between wild-type measles exposure and when the serum specimen is obtained, the detection of measles-specific IgG in an asymptomatic contact after measles exposure is representative of pre-existing immunity. Detection of measles-specific IgG does not always correlate with a protective antibody response; secondary vaccine failure (i.e., measles infection despite pre-existing immunity) does occur, but this is rare and generally associated with prolonged and intense contact to a measles case.

Plaque reduction neutralization assay (PRN)

The most definitive serologic evidence of recent measles infection is a four-fold rise in titer between acute and convalescent serum samples as measured in a measles virus plaque reduction neutralization assay (PRN). Unlike the IgG EIA, this test measures measles functional (neutralizing) antibodies, requires specialized reagents, and is labor and time intensive. Most cases will not require this testing; prior approval for these tests should be obtained from the CDC Measles Laboratory.

IgG Avidity

A single acute-phase serum sample can be tested for IgG avidity, as long as the sample has detectable IgG. Low avidity IgG confirms a recent measles infection (or recent vaccination) in cases without prior history of vaccination or infection. Avidity testing can also distinguish between primary and secondary vaccine failures. Avidity testing requires specialized reagents, and its use is limited to unusual cases, usually for highly suspicious sporadic cases or in an outbreak setting when cases with modified or nonclassical presentation of measles are detected. Prior approval for IgG avidity testing must be obtained from the CDC Measles Laboratory.

Measles RNA detection (rRT-PCR)

Clinical specimens for rRT-PCR should be collected at the same time as samples taken for serologic testing. Sensitivity is highest for rRT-PCR within the first three days of rash onset, but measles virus can be detected up to ten days after rash onset. Efforts should be made to obtain a throat (OP) or nasopharyngeal (NP) swab from suspected cases with rash onset at first contact. Urine samples may also contain measles virus, and when feasible to do so, collection of both respiratory and urine samples can increase the likelihood of detecting measles virus. Detection of measles RNA by rRT-PCR in clinical specimens confirms the diagnosis of measles, unless there has been recent vaccination (see "Recently Vaccinated Persons" below). Detection of measles RNA by rRT-PCR in the clinical sample is particularly helpful for case confirmation when serology results are inconclusive.

rRT-PCR is highly sensitive, but a negative test may not rule out measles, especially when there is strong clinical suspicion, because the test is affected by the timing of specimen collection and the quality and handling of clinical specimens. A poorly collected or poorly maintained specimen may be falsely negative. Therefore, a negative test should be interpreted in the clinical and epidemiologic context of the case to make a determination about the likelihood of measles infection.

Measles Vaccine (MeVA) Assay

The Measles Vaccine (MeVA) Assay, available at the CDC and the APHL-VPD Reference Centers, is available to rapidly determine if detected measles virus is vaccine-derived or wild-type virus, if necessary. The MeVA assay is a rRT-PCR assay that detects measles vaccine strains and is performed in conjunction with a standard rRT-PCR assay that detects all measles strains. Rapid identification of measles vaccine reactions may be needed in an outbreak setting where an individual was recently exposed (i.e., within 21 days of rash onset) to wild type-measles but also was recently vaccinated.

Measles Virus Sequencing (Genotyping)

Molecular epidemiologic surveillance provides critical data that can support a link (or lack thereof) of cases or outbreaks to each other or to source countries. Sequencing is used to track transmission pathways and to document the absence of endemic circulation of measles in the United States.41 Sequencing also can distinguish between wild type virus infection and a rash caused by a reaction to measles vaccine strain virus.

Laboratory Evaluation of Suspect Measles Cases

Testing for all suspect measles cases should ideally include both serologic testing and rRT-PCR to optimize sensitivity and specificity of testing.

Unvaccinated Persons (or persons with unknown immunity)

Following measles virus infection in an unvaccinated individual, measles IgM antibodies appear within the first few days (1–4 days) of rash onset and peak within the first week after rash onset. IgM tests may be falsely negative if serum is collected within 72 hours after rash onset given variable appearance of IgM; if a negative result is obtained from serum collected within 72 hours after rash onset, a second serum should be collected ≥72 hours after rash onset.42 Concurrent testing with serology and viral detection (e.g., rRT-PCR) can mitigate the impact of early false negative IgM, as the first 72 hours after rash onset is the optimal time period for rRT-PCR sensitivity. Measles IgM may be detectable for up to 6–8 weeks after rash onset.

Measles IgG antibodies are generally produced and detectable a few days after the IgM response. The timing of IgM and IgG response varies among individuals, but IgG should be detectable by 7–10 days after rash onset. IgG levels peak approximately two weeks post rash onset and generally persist for life.

If classification of a case cannot be made after testing a serum sample collected ≥72 hours after rash or detection of measles virus was not successful, a convalescent serum sample can be collected 10–30 days after the acute serum specimen for testing by plaque reduction neutralization (PRN) or other quantitative tests validated for this use. Avidity testing may also be helpful in these situations, as low avidity IgG would confirm recent exposure to measles virus.

Persons with Pre-existing Immunity (vaccinated or with prior history of infection)

Measles infection in persons with pre-existing immunity can be challenging to recognize clinically and difficult to characterize serologically. Individuals who have been previously exposed to measles antigen may have a modified disease presentation, with absent or atypical rash presentation. These cases are usually detected during an outbreak or after a known exposure to a confirmed measles case. However, in rare instances, such cases can occur without a known exposure or other risk factor.

Among persons with pre-existing immunity, the IgM response may be delayed, transient, or absent, and the immune response may be characterized by a rapid and robust IgG response.43 Therefore, rRT-PCR testing may be the best method to confirm cases among persons with pre-existing immunity. If initial tests for IgM are negative, a second serum sample may be collected 5–10 days later; if this specimen remains IgM negative, then paired serum samples collected >10 days apart can be tested by PRN assay (or other assay quantitative validated for this use), as described above.

IgG avidity testing can also be useful in evaluating previously vaccinated persons with suspect measles. Low IgG avidity suggests recent measles infection or recent measles vaccination, while high IgG avidity characterizes response to remote vaccination or prior measles infection. IgG avidity can be used to differentiate primary versus secondary vaccine failure (see Chapter 22, Table 5).

Recently Vaccinated Persons

Vaccination with MMR or MMRV can result in fever in up to 15% of recipients and a self-limited rash in up to 5% of recipients approximately 6–12 days after vaccination. Therefore, it is important to rapidly determine whether clinical symptoms in recently vaccinated persons are caused by a measles infection or by a vaccine reaction. Patients presenting with vaccine reactions may also have cough, coryza, or conjunctivitis, and therefore meet the measles clinical case definition.44 In the absence of a known measles risk factor (e.g., international travel, domestic travel to a region with ongoing measles transmission, or known contact with a measles case), further testing for measles infection is usually not necessary and the symptoms can likely be attributed to a vaccine reaction. The most common scenario where further evaluation is required are among those who receive MMR vaccination as postexposure prophylaxis following exposure to measles or in the setting of a community outbreak.

To differentiate measles infection from a vaccine reaction, the MeVA assay can be performed and can rapidly differentiate measles infection from a vaccine reaction. Genotyping can also distinguish between vaccine-derived and wild-type measles virus. The measles component of MMR or MMRV is generally detectable for up to 21 days after vaccination, although vaccine-strain virus can be detected >21 days after vaccination in some instances.

When a patient with suspected measles has been recently vaccinated (6–45 days prior to blood collection), neither IgM nor IgG antibody responses can distinguish measles disease from the response to vaccination. Following vaccination, measles IgM may not be detectable until 8–14 days after vaccination and measles IgG may not be detectable for up to three weeks after vaccination.45

Ruling out a false positive IgM by testing a second serum sample

Testing for measles-specific IgM, even from persons with rash and fever, can produce false positive IgM results. If the acute serum sample was IgG negative, and rRT-PCR is not available to provide additional information regarding case classification, a second serum specimen can be collected at ≥10 days after the acute sample. If this second serum sample is IgG negative, measles can be ruled out. If the acute serum was IgG positive, a second serum, collected ≥2 weeks after the acute specimen, can be tested for a significant (usually four-fold) rise in IgG between paired specimens using a validated, quantitative IgG assay (e.g., PRN).

Commercial Laboratory Testing

Many commercial laboratories offer measles serologic testing, including IgM and IgG. When testing for acute measles, both IgM and IgG testing is recommended. When testing for evidence of measles immunity, measles IgG alone should be completed; measles IgM testing among asymptomatic individuals without risk factors for measles infection would be expected to return only false positive results.

Some commercial laboratories are also beginning to offer measles rRT-PCR testing. Commercial laboratory testing does offer some advantages, including integration with standard test routing and integration with electronic medical record systems. However, use of commercial laboratories can limit the awareness of public health authorities regarding suspect measles cases; providers should consider alerting their public health jurisdiction regarding suspect measles cases. All rRT-PCR positive specimens must be submitted to an APHL-VPD Reference Center or CDC for sequencing; however, commercial laboratories may not store specimens appropriately or for long enough for additional testing to occur.

Specimen collection

Specimen collection and shipping are important steps in obtaining laboratory diagnosis or disease confirmation. Guidelines have been published for specimen collection and handling for viral and microbiologic agents. Specific instructions for specimen collection and shipping for measles specimens may be obtained from the CDC measles website or by contacting the CDC Viral Vaccine Preventable Diseases Branch at 404-639-4181. Specimens for virus isolation and sequencing should be sent to CDC as directed by the State Health Department.

General information is also available on using CDC laboratories as support for reference and disease surveillance; this includes:

• A central website for requesting lab testing;
• The form required for submitting specimens to CDC (See Form # CDC 0.5034);
• Information on general requirements for shipment of etiologic agents (see Appendix 24)—although written to guide specimen submission to CDC, this information may be applicable to submission of specimens to other laboratories; and
• The CDC Infectious Diseases Laboratories Test Directory, which not only contains a list of orderable tests for that institution, but also detailed information such as appropriate specimen types, collection methods, specimen volume, and points of contact.

The APHL/CDC Vaccine Preventable Disease Reference Centers perform RT-PCR to detect measles RNA and measles sequencing.

For additional information on use of laboratory testing for surveillance of vaccine-preventable diseases, see Chapter 22, "Laboratory Support for the Surveillance of Vaccine-Preventable Diseases."

Reporting and Case Notification

Case reporting within a jurisdiction

Each state and territory has regulations or laws governing the reporting of diseases and conditions of public health importance.46 Measles is nationally notifiable and should be reported in a timely manner to state or local health departments; the specific requirements for reporting may differ by state.47

Case notification to CDC

Since continuous endemic measles transmission has been eliminated, measles is an immediately notifiable disease. Measles cases should be reported promptly (within 24 hours³) by the state health department to the CDC directly by e-mail (measlesreport@cdc.gov). Notifications of confirmed cases using the event code 10140 should then be electronically reported by the state health department to the National Notifiable Diseases Surveillance System (NNDSS) with the next regularly scheduled electronic transmission.

³CSTE List of Nationally Notifiable Diseases [2 pages]

Information to collect

The following data are epidemiologically important and should be collected during case investigation. Additional information also may be collected at the direction of the state health department.

For an example line list and case investigation form that can be used to track cases and contacts, please see: CDC Measles Public Health Professionals Webpage.

Demographic information

• Name
• Address
• Date of birth
• Age
• Sex
• Ethnicity
• Race
• Country of birth
• Residency (e.g., Does the case reside in the United States or is a foreign visitor?)

Reporting source

• State
• County
• Date first reported to a health department

Clinical

• Pregnancy status (if applicable)
• Date of onset of symptoms
• Date of rash onset
• Prodromal symptoms (i.e., cough, coryza, conjunctivitis, fever [note highest temperature])
• Rash duration
• Complications (including dehydration, diarrhea, otitis media, pneumonia)

Outcomes

• If hospitalized
  • Date of hospitalization
  • Reason for hospitalization (if known)
  • Duration of hospitalization
• If deceased:
  • Date of death
  • Results of postmortem examination
  • Death certificate diagnoses

Laboratory

• Serological tests
  • Type of specimen (IgM, IgG, avidity, PRN)
  • Date of collection of specimen
  • Results
• Molecular tests
  • Type of specimen (e.g., rRT-PCR) and source (i.e., throat/NP swab, urine)
  • Date of collection of specimen
  • Results

Vaccination status (including postexposure prophylaxis)

• Number of doses of measles vaccine received
• Dates of measles vaccinations
• If not vaccinated, reason
• Postexposure prophylaxis type (vaccine, IGIV, IGIM)
• Date of administration of postexposure prophylaxis

Epidemiological

• Transmission setting (e.g., household, school, health care setting, event)
• Source of infection (e.g., age, vaccination status, relationship to case, contact with probable or confirmed case, or contact with immigrants or travelers, or international travel)
• Import status (international import or U.S.-acquired case, see section "Case Definition")
• Travel history in the three weeks prior to symptom onset, including flight or maritime information
• Date of return to United States
• Number of contacts

Importance of Rapid Identification and Surveillance

Prompt recognition, reporting, and investigation of measles are important because the spread of the disease can be limited with early case identification and vaccination of susceptible contacts.

Confirmed and suspect case identification

Suspect measles cases should be rigorously evaluated by clinical and public health partners to ensure early case identification. Early notification to state or local public health partners can facilitate diagnosis and rapid implementation of control measures if the case is confirmed. In the case of suspected measles in the context of recent vaccination (see "Laboratory Testing" section above), investigation and control measures should be implemented until measles infection, or a vaccine reaction can be confirmed. A systematic review of published literature found no reported confirmed instances of human-to-human transmission of the measles vaccine virus; therefore, control measures may be stopped once a vaccine reaction, or detection of vaccine strain virus, is confirmed.48

Active surveillance for additional measles cases should be conducted for every confirmed measles case to assure timely reporting of suspected cases in the population known to be affected, including other segments of the community that may be at high risk of exposure or in whom vaccination coverage is known to be low. Efforts should be made to obtain clinical specimens for viral detection for all suspect measles cases that are identified (see "Laboratory Testing" section above). Active surveillance should be maintained until at least two incubation periods after the last confirmed case is reported (e.g., two maximum incubation periods [21 days from exposure to rash] or 42 days after rash onset in last case).

If the case-patient was traveling by plane or ship or across a land border during the infectious period, the CDC Port Health Station (under the Division of Global Migration Health) with jurisdiction for the reporting state should be contacted for assistance in the investigation and contact tracing of potentially exposed passengers and crew. If unable to contact the Port Health Station, call the Emergency Operations Center (EOC) at 770-488-7100 for assistance. Information that should be collected and shared with DGMH includes date(s) of travel, departure and arrival locations, and flight or ship carrier and number.

Enhancing surveillance

Because measles importations occur every year in the United States, additional surveillance effort may be required to ensure that appropriate and timely diagnosis of rash illnesses and reporting of suspected cases continues. In addition, the rapid investigation and reporting of all suspected cases and recording of vaccination history and import status for all cases has become increasingly important.

Additional guidelines for enhancing surveillance are given in Chapter 19, "Enhancing Surveillance."

Monitoring surveillance indicators

Regular monitoring of surveillance indicators, including time intervals between diagnosis and reporting and completeness of reporting, may identify specific areas of the surveillance and reporting system that need improvement. An important indicator of the adequacy of the measles surveillance system is the detection of importations. In the absence of measles endemic transmission, imported cases or cases linked to importations should be detected. A program which reports no imported cases in settings where endemic measles has been eliminated cannot be assumed to have adequate measles surveillance. For more information on surveillance indicators, see Chapter 18, "Surveillance Indicators."

The following indicators should be monitored:

• The proportion of confirmed cases reported to the NNDSS with complete information
• The median interval between rash onset and notification of a public health authority, for confirmed cases
• The proportion of confirmed cases that are laboratory confirmed
• The proportion of cases that have an imported source
• The proportion of cases for which at least one clinical specimen for virus isolation was collected

Case and Contact Investigation

All reports of suspected measles cases should be investigated immediately.

In the measles post-elimination era, a single reported case of measles is considered a public health priority that requires rapid and appropriate public health response; additional effort is required to ensure that appropriate and timely diagnosis of rash illnesses and reporting of suspected cases continues in order to prevent outbreaks and re-establishment of endemic disease transmission.

The CDC Measles Public Health Professionals Webpage has an example line list and case investigation form which can be used as a guideline for collecting demographic and epidemiologic data during case and contact investigations. Essential components of case investigation include establishing a diagnosis of measles, obtaining immunization histories for confirmed cases, identifying sources of infection, assessing potential for transmission, and identifying contacts without presumptive evidence of immunity, classifying importation status, and obtaining specimens for genotyping.

As measles continues to be endemic in many regions of the world, importations of measles occur every year in the United States. Each imported measles case could result in transmission of measles to susceptible individuals if exposed. Surveillance and prompt investigation of cases and their susceptible contacts is important because the spread of the disease can be limited with early case identification and public health response including vaccination and quarantine of susceptible contacts without presumptive evidence of immunity. However, because some imported measles cases are not detected in our surveillance system, maintaining a high alertness for measles is needed since not every "sporadic" case occurring in the community can be linked to an importation.

Information obtained through surveillance is also used to describe current measles epidemiology and to evaluate prevention policies. Surveillance data are used to characterize persons, groups, or areas in which additional efforts are required to reduce risk of measles disease and outbreaks.

Identify cases and establish a diagnosis

An essential first step in a measles case investigation is to obtain necessary clinical information to determine whether a reported case is clinically compatible with measles and to obtain key epidemiological information. However, public health action, if needed, should not be delayed while awaiting case confirmation if measles is suspected based on initial investigations. Suspected cases of measles should have laboratory confirmation and efforts should be made to obtain clinical specimens for viral testing (see "Laboratory Testing").

In the measles post-elimination era, most cases of febrile rash illness seen in physician's offices that meet the clinical case definition will not be measles. Common childhood illnesses such as Parvovirus B-19 and HHV-6 (Roseola) presents as febrile rash illnesses and have been implicated in prior false positive evaluations for measles in post-elimination settings.37 However, health care providers should maintain a high index of suspicion for measles in clinically compatible cases, especially among unvaccinated persons and among persons who recently traveled abroad or who have had contact with persons such as travelers or international visitors. The CDC Measles Public Health Professionals Webpage has an example clinical decision flowsheet which can provide guidance on whether or not measles testing may be warranted; jurisdictions can adapt this flowsheet to meet the needs of their healthcare providers and health systems.

It is important to consider measles in the differential diagnoses of patients under evaluation for febrile rash illnesses, including parvovirus, dengue, Kawasaki disease, and scarlet fever. In addition, when evaluating patients with suspected measles who have negative tests for acute measles infection, additional testing for rubella can be considered.

Obtain accurate and complete immunization histories

Measles case investigations should include complete immunization histories that document all doses of measles-containing vaccine. Acceptable proof of vaccination is documented administration of live measles virus-containing vaccine. Written or electronic records (including electronic medical records) with dates of vaccine administration are the only acceptable evidence of vaccination. Case-patients or their caregivers may have personal copies of immunization records available that include dates of administration; these are acceptable for reporting purposes. Usually, immunization records must be sought from review of childcare or school/college records or from providers; if the case works in a health care setting, immunization records may be available at the health care facility. Immunization registries are now very useful sources of vaccination histories for children and adolescents.

As part of the initial case investigation, case-patients or their parents should be asked where all vaccines were received, including the names of private physicians and out-of-town or out-of-state providers. Records at public health departments and health centers should be reviewed, and private physicians should be contacted and asked to review patient records for this information. With careful planning in an outbreak setting, it is possible to contact providers with a list of all case-patients reported to date for whom data are needed, and to call back at a prearranged time, rather than repeatedly contacting providers for records on individual children.

Measles vaccination is available in the United States only as part of MMR (measles-mumps-rubella) and MMRV (measles-mumps-rubella-varicella) but is available internationally as part of MR (measles-rubella) and M (measles alone) formulations. All confirmed case-patients should then be classified as recipients of one dose of measles-containing vaccine (as MMR, MMRV, MR or M), two doses, three or more doses, or no doses of vaccine. The date of vaccination for each dose and the interval between doses should be noted.

Written documentation of the date of administration are the only doses that are considered to be valid; self-reported doses and history of vaccination is not valid. The vaccination status of persons for whom vaccination status cannot be verified should be classified as unknown. Persons are categorized as unvaccinated if they report that they had no history of being vaccinated; if available, immunization records should be checked to verify lack of vaccine receipt.

Identify the source of infection

Efforts should be made to identify the source of infection for every confirmed case of measles. Case-patients or their caregivers should be asked about contact with other known cases. When no history of contact with a known case can be found, opportunities for exposure to unknown cases should be sought. Such exposures may occur in schools, during air travel, through other contact with recent travelers or foreign visitors, while visiting tourist locations (casinos, resorts, theme parks), in health care settings, or in churches. Unless a history of exposure to a known case within 7–21 days prior to onset of rash in the case is confirmed, case-patients or their caregivers should be closely queried about all these possibilities.

Assess potential for transmission and identify contacts without presumptive evidence of immunity

In the event of a confirmed measles case, local or state health departments should contact health care providers in their areas through the media or Epi-X to inform them of the confirmed case and request immediate reporting of any suspected cases. Previously unreported cases may be identified by reviewing emergency room logs, electronic medical records, or laboratory records. Hospital emergency rooms and physicians serving affected communities are usually recruited to participate in active surveillance.

General guidelines

Tracking what information is collected and what still needs to be collected. Tracking is easily accomplished by constructing a line listing of cases, allowing ready identification of known and unknown data and ensuring complete case investigation. The line listing is an essential component of every outbreak investigation (see CDC Measles Public Health Professionals Webpage).

Identifying risk of transmission in the population affected by the outbreak. As part of the case investigation, the potential for further transmission should be evaluated, and an assessment should be made of exposed contacts of the case-patient during the case patient's infectious period (four days before to four days after rash onset) and the presumptive evidence of immunity of all contacts. In a closed setting the measles virus has been reported to have been transmitted by airborne or droplet exposure up to two hours after the measles case occupied the area.49

Based on the findings of individual case investigations, the population affected by the outbreak should be characterized in terms of

• person (who is getting measles and how many case-patients have had zero, one, and two doses of measles vaccine?),
• place (where are the cases?), and
• time (when did it start and is it still going on?). (For more information on data analysis, see Chapter 20, "Analysis of Surveillance Data.")

These essential data elements allow public health officials to

• identify the population at risk of infection (e.g., unvaccinated preschool-age children, high school students who have only received one dose of measles vaccine, persons who visited the emergency room of Hospital A on a certain day);
• determine where transmission is occurring or likely to occur (transmission is particularly likely in households, daycare, schools, health care settings, and in congregate settings such as churches and other institutions [colleges, prisons, etc.]); and
• identify persons who are at highest risk of infection or transmission (other unvaccinated children, students attending other schools, immunocompromised persons, pregnant women, health care personnel, infants aged <12 months etc.).

Control Measures

In general, the most effective control efforts are those that are targeted based upon epidemiologic data, rather than those that are directed at the entire community. Neither susceptibility nor risk of exposure is uniformly distributed throughout the community, and resources available for control may be limited. Therefore, it is essential that data be used to determine the scope of the investigation and the potential for spread and that intervention be based on those determinations using public health judgment to guide investigation and control efforts. The primary strategy is achieving a high level of immunity in the population affected.33

Initiation of investigation and prioritization of contacts

State and local health departments should use their judgment to prioritize such investigations according to epidemiology and identified transmission settings. Settings at highest risk of transmission based on the epidemiology of the outbreak may be prioritized for public health response.

If suspected and probable cases are investigated, postexposure prophylaxis of household contacts without presumptive evidence of immunity should not be delayed pending the return of laboratory results. Other high priority groups for contact investigation are 1) close contacts other than household (e.g., persons who share the same room or airspace in various settings), 2) healthcare settings because of the risk of transmission to persons at high-risk of serious complications, and 3) schools/child care centers, colleges or other close settings (e.g., churches) where a defined number of persons have congregated because of high contact rates and transmission potential. In all these settings, exposures usually result in an identified number of susceptible contacts to follow up on individually. However, efforts to identify the likelihood of exposure in larger settings such as hospitals (e.g., patients and health care personnel in emergency departments) may be helpful. In particular, one should identify individuals at high risk for severe disease including infants who are not vaccinated, immunocompromised individuals, and pregnant people.

Initial preparation for major control activities may need to be started before the laboratory results are known. However, it is reasonable to delay major control activities, such as checking presumptive evidence of immunity and enforcing student exclusion, pending the return of laboratory results, which should be obtained as quickly as possible (within 24 hours).

If resources are constrained, other exposure settings will more commonly be lower priority to investigate, though public health decisions should be guided by the epidemiologic investigation. For exposures at such venues as restaurants, stadiums, and malls, communicating with the general public through radio, TV, Epi-X, or other media, may be used to reach potentially exposed persons rather than individual contact tracing. Persons can be guided to their physicians or the health department for assessment of immunity status and the need for vaccination.

Additional guidelines for enhancing surveillance are given in Chapter 19, "Enhancing Surveillance."

Isolation of cases and exclusion of contacts without presumptive evidence of immunity

Case-patients without immunocompromising conditions should be isolated for four days post rash onset. Isolation of persons with immunocompromising conditions may need to be prolonged due to the risk of prolonged viral shedding, and determination of isolation should be made on a case-by-case basis.33

Exposed persons who cannot readily document presumptive evidence of measles immunity should be offered postexposure prophylaxis (PEP) or excluded from the setting (school, hospital, day care). For assessment of presumptive evidence of immunity of contacts, only doses of vaccine with written documentation of the date of receipt should be accepted as valid. Verbal reports of vaccination without written documentation should not be accepted.

Persons who have been exempted from measles vaccination for medical, religious, or other reasons and who do not receive appropriate postexposure prophylaxis within the appropriate time should be excluded from affected institutions in the outbreak area until 21 days after the onset of rash in the last case of measles.

Quarantine and its use

Quarantine (most commonly voluntary quarantine) of exposed persons has been implemented especially where unvaccinated or populations at high risk were affected. In such situations, quarantine has helped to contain the spread of the disease to the surrounding community.18505152 Compliance with quarantine can be ensured at the discretion of the health department. When deciding about quarantine, factors to consider include:

• Immune status of the individual,
• Presumptive evidence of immunity,
• Whether the person is at high risk of acquiring measles based on exposure characteristics, and
• Transmission settings.

In general, quarantine should be prioritized for those with clear, prolonged exposure to a measles case and should be implemented for people without evidence of any protective immunity to measles. Imposing quarantine measures for outbreak control may be difficult and disruptive to individuals and institutions; however, given that transmissibility of measles can occur prior to development of symptoms that clearly represent measles (i.e., during the nonspecific prodromal period), quarantine may be required to prevent spread of measles within communities.

Postexposure vaccination and use of immunoglobulin to prevent measles in exposed susceptible persons

Presumptive evidence of measles immunity should be assessed for all identified contacts. Use of postexposure prophylaxis (PEP), available either in the form of MMR vaccine or immunoglobulin (IG), may prevent or modify the clinical course of disease among susceptible persons. Overall, estimates of PEP effectiveness are limited and mixed; effectiveness appears to depend on the timing of PEP administration and the nature of exposure.33 Individuals who receive PEP should be monitored for signs and symptoms consistent with measles for at least one incubation period.

Infectious or potentially infectious persons requiring medical attention (e.g., a susceptible contact in quarantine who develops measles-like symptoms), should be advised to call ahead before visiting a clinic or emergency department to ensure appropriate precautions are in place prior to the medical encounter.

Use of MMR as PEP

The MMR vaccine, if administered within 72 hours of initial measles exposure, may provide some protection or modify the clinical course of disease among susceptible persons who otherwise have no contraindications to MMR vaccination (e.g., severe immunocompromise, age <6 months, pregnancy).33 However, vaccination should be offered at any interval following exposure to offer protection from future exposures. All doses of live vaccine should be separated by 28 days or more; if a live vaccine other than MMR (e.g., varicella) was received within the 28 days prior to need for PEP, the risks and benefits of MMR vaccination should be weighed.

Except in health care settings, susceptible persons who receive a dose of MMR as PEP within 72 hours of initial measles exposure may return to childcare, school, or work.

Any susceptible contact under 12 months of age who receives MMR vaccination should be revaccinated according to the routine pediatric schedule (i.e., two additional doses with the first between 12–15 months of age); all doses of MMR must be separated by at least 28 days.

Use of IG for PEP

IG, if administered within six days of initial measles exposure, may provide some protection against measles or modify the clinical course of disease among susceptible persons.33 IG is the only option for PEP for populations which cannot receive MMR (infants less than six months of age, severely immunocompromised people, and pregnant people). IG can be administered intramuscularly (IMIG) or intravenously (IVIG). IMIG is recommended for infants <12 months of age (dose 0.5mL/kg; maximum dose = 15mL), and IVIG is recommended for severely immunocompromised people and pregnant people who are exposed to measles (dose 400mg/kg). Priority should be given to persons exposed in settings with intense, prolonged, and close contact (e.g., household, daycare, classroom) and for those at high risk of severe disease. IG PEP should be provided to severely immunocompromised contacts regardless of prior measles vaccination status due to the risk for severe disease.

IG PEP can be given to susceptible infants aged 6–12 months, although MMR is preferred per AAP guidance if received within 72 hours of exposure.53 AAP does not recommend routine use of IG PEP for immunocompetent children >12 months of age; ACIP guidance allows for consideration of IG PEP during days 4–6 after exposure for immunocompetent susceptible contacts ≥12 months of age, although IG PEP is not commonly used for these contacts given a lower risk of severe outcomes in this age group.33 For exposed persons without evidence of measles immunity, serology (IgG antibody test) can be used to inform immune status, provided that administration of IG PEP is not delayed.

Use of IMIG PEP for immunocompetent contacts aged ≥12 months may also be limited because of volume limitations. The recommended dose of IMIG is 0.5mL/kg of body weight. IM injections are limited to maximum volumes that depend on age and body weight but are typically limited to ≤3mL per injection for pediatric populations. Therefore, IMIG for people weighing >6kg will likely require more than one injection, which can be distressing for patients, families, and caregivers.54 Additionally, the dose of IMIG for people weighing >30kg would exceed the maximum dose of 15mL, and would therefore not be expected to provide adequate titers for protection.

Receipt of IG PEP may prolong the duration of the incubation period of measles; the symptom monitoring period should therefore be increased to 28 days for those receiving IG PEP.55 Increasing the length of the quarantine period for contacts who have received IG PEP is at the discretion of the health department. After receipt of IG PEP, persons should be excluded from health care settings.55 In other settings such as childcare, school, or workplaces, factors such as the individual's immune status, intense or prolonged contact, and presence of populations at risk for measles should be taken into consideration when weighing the risks and benefits of exclusion for those receiving IG PEP. These factors may decrease the effectiveness of IG PEP or increase the risk of disease and complications depending on the setting to which the contact may be returning.

Any nonimmune person exposed to measles who received IG PEP should subsequently receive MMR vaccine, which should be administered no earlier than six months after IMIG or eight months after IVIG, provided the person is then ≥12 months of age and the vaccine is not otherwise contraindicated.

IG PEP should not be used to control measles outbreaks, but rather to reduce the risk for infection and complications in the person receiving it.

Role of community-wide vaccination efforts in outbreak control

Physicians in affected communities should use the opportunity of a confirmed measles case for reminder/recall to ensure that all their patients are up to date with MMR vaccine requirements. Community-wide vaccination clinics are rarely indicated but targeted clinics may be held to reach affected populations (e.g., vaccination for health care workers, a work setting clinic with affected adults, or offering clinics at health departments in under-immunized communities).

For outbreaks with sustained, community-wide transmission affecting preschool-aged children or adults and with ongoing risk of exposure, health departments may consider an early second dose for children aged one through four years or adults in these affected areas (including visitors) who have received one dose. Of note, all doses of MMR must be separated by at least 28 days.

For outbreaks with sustained, community-wide transmission affecting infants <12 months of age and with ongoing risk of exposures to infants, health departments may consider vaccination of infants aged 6–11 months in these affected areas (including visitors) with one dose of MMR vaccine. This recommendation should be made following careful assessment of the benefit of early protection against measles during a period of increased transmission and exposure, and risk of decreased immune response following subsequent MMR doses in infants vaccinated at <12 months of age compared with infants vaccinated at ≥12 months of age.5657 Decisions to vaccinate infant visitors <12 months of age should follow local health department guidance of the affected area (e.g., if no recommendation was made to vaccinate infant residents, vaccination of infant visitors is not recommended). This dose does not count as one of the two recommended doses; infants who receive one dose of MMR vaccine before their first birthday should receive two more doses according to the routinely recommended schedule (one dose at 12 through 15 months of age and another dose at 4 through 6 years of age or at least 28 days later).33

Day care centers, schools and other educational institutions

Measles cases in schools, colleges, and other institutions, such as day care centers and camps where close contact may exist, require rapid public health investigation for response and for evaluation of risk of further transmission. In educational institutions where a high proportion of students are unvaccinated, the potential risk of spread of the disease is high. Two doses of MMR is recommended at time of school entry, and for all students in post-secondary educational settings.33 Control measures include the following actions:

• Exclusion and isolation of cases (they can return on the fifth day after rash onset if not immunocompromised)
• Offering vaccine for those who are not up-to-date with age-appropriate vaccination (first dose to unvaccinated, second dose to those with one documented dose can be given at least 28 days after the first dose)
• Immunoglobulin if pregnant or immunocompromised
• Persons who continue to be exempted from or who refuse measles vaccination should be excluded from the school, childcare, or other institutions until 21 days after rash onset in the last case of measles.5058

All students and all school personnel born in or after 1957 who cannot provide adequate presumptive evidence of immunity should be vaccinated. Persons receiving their second dose and previously unvaccinated persons receiving their first dose appropriately (i.e., before, or within 72 hours of, exposure) as part of the outbreak control program may be immediately readmitted to school. However, these individuals should be monitored for signs and symptoms of measles.

Day care centers, school, and other educational institutions can prepare for measles cases and outbreaks. Having accurate and up-to-date data on vaccination coverage within an educational institution can assist administrators and public health officials during the response to a measles case or outbreak in a facility. Institutions can consult with public health authorities to develop measles outbreak response plans. Finally, institutions can draft exposure letters in advance to inform parents and staff about measles exposures, should they occur in the future.

Health care settings

Persons who work in health care settings (including volunteers, trainees, nurses, physicians, technicians, receptionists, and other clerical and support staff) are at increased risk of exposure to measles and at increased risk of transmission to persons at high risk of severe measles. All persons who work in such settings and have the potential for exposure to potentially infectious patients or materials (e.g., contaminated air) should have presumptive evidence of immunity to measles to prevent any potential outbreak.2255

Presumptive evidence of immunity and routine vaccine recommendations for health care personnel

Health care personnel (HCP) have slightly different criteria for acceptable presumptive evidence of immunity. All HCP should have presumptive evidence of immunity to measles.2255 This information should be documented and readily available (ideally through electronic medical records) at the work location.

Presumptive evidence of immunity to measles for health care personnel includes any of the following:

• Written documentation of vaccination with 2 doses of live measles or MMR vaccine administered at least 28 days apart,*
• Laboratory evidence of immunity,^†
• Laboratory confirmation of disease, or
• Birth before 1957.^‡

Although birth before 1957 is considered as presumptive evidence of immunity, for unvaccinated HCP born before 1957 that lack laboratory evidence of measles immunity or laboratory confirmation of disease, health care facilities should consider vaccinating personnel with two doses of MMR vaccine at the appropriate interval.

*The first dose of measles-containing vaccine should be administered on or after the first birthday; the second dose should be administered no earlier than 28 days after the first dose.

^†Measles immunoglobulin (IgG) in the serum; equivocal results should be considered negative. Documentation of two age-appropriate MMR doses supersedes the results of serologic testing.55

^‡The majority of persons born before 1957 are likely to have been infected naturally and may be presumed immune, depending on current state or local requirements. For unvaccinated personnel born before 1957 who lack laboratory evidence of measles immunity or laboratory confirmation of disease, health care facilities should consider vaccinating personnel with two doses of MMR vaccine at the appropriate interval. For unvaccinated personnel born before 1957 who lack laboratory evidence of measles immunity or laboratory confirmation of disease, health care facilities should recommend two doses of MMR vaccine during an outbreak of measles.

Prevention and control strategies in medical settings

An effective vaccination program is the best approach to prevent health care associated measles transmission. Ensuring that healthcare personnel (HCP) have presumptive evidence of immunity is recommended to prevent measles transmission in healthcare settings. It is important to note that while birth year before 1957 is broadly considered presumptive evidence of immunity, this is not true for HCP during measles outbreaks in healthcare settings. The Health Care Infection Control Practices Advisory Committee (HICPAC) and CDC have recommended that secure, preferably computerized, systems should be used to manage vaccination records for HCP so records can be retrieved easily as needed.55 Failure to have such records can be costly and can increase resources needed to respond to the outbreak.59

Minimizing potential measles exposures in healthcare settings requires multiple interventions. In medical settings, both the occupation health and infection prevention and control practitioners have a role. Prevention can occur before arrival to the healthcare setting (e.g., notifying the facility of concern for measles, if known) through use of prompt isolation and avoidance of common areas (e.g., waiting rooms).

Measles is thought to be contagious to others in the air for up to a maximum of two hours after a person with measles leaves the airspace. Determining how long a space may be considered infectious to others can depend on several factors including the room's air changes per hour, humidity, and air flow dynamics between rooms. For additional information on defining occupational measles exposures, see: Measles Infection Control in Healthcare Personnel (section: Occupational Exposures) and the CDC Airborne Contaminant Removal Table.

If a measles case is identified in a healthcare setting, including outpatient and long-term care facilities, the following measures should be taken:

• Implementation of airborne and standard precautions for patients in whom measles is suspected or confirmed.60
• Airborne precautions include isolation in a negative air pressure isolation room, also known as airborne infection isolation (AII) or airborne infection isolation room (AIIR). In clinic settings where a negative air pressure isolation room may not be available, a single room with the door closed and away from susceptible contacts may be used when evaluating persons in whom measles is suspected while arranging transfer to a facility where an AIIR is available.
• In addition, suspect or confirmed measles patients should be asked to wear a medical mask.55
• Immediate review of evidence of measles immunity in all exposed HCP and exposed patients.
• Management of healthcare personnel without presumptive evidence of immunity (see below).

For HCP with presumptive evidence of immunity to measles, postexposure prophylaxis and work restrictions are not necessary. Daily symptom monitoring should be implemented from the 5^th day after first measles exposure through the 21^st day after the last measles exposure, with awareness that previously vaccinated individuals may have a modified disease presentation.

For HCP without presumptive evidence of immunity to measles, the following guidelines apply:

• HCP should be assessed for eligibility for postexposure prophylaxis in accordance with ACIP guidelines.33 Receipt of PEP does not alter exclusion recommendations for HCP.
• HCP with no prior documented doses of MMR should be offered the first dose of MMR vaccine and should be excluded from work from day 5 after the first measles exposure to day 21 following their last exposure. HCP without evidence of immunity should receive vaccination in accordance with ACIP recommendations.55
• HCP who received a single dose of MMR vaccine prior to exposure may remain at work and should receive the second dose of MMR vaccine, at least 28 days after the first dose.
• All HCP without presumptive evidence of immunity should receive daily monitoring of signs and symptoms of measles from the 5^th day after their first exposure through the 21^st day after their last measles exposure.
• Healthcare facilities should provide MMR vaccine to all personnel without presumptive evidence of measles immunity at no charge.

For additional details on management of healthcare personnel exposed to measles, see: Measles Infection Control in Healthcare Personnel.

Because of the possibility, albeit low, of measles vaccine failure in HCP, all staff entering the room of a person with suspect or confirmed measles should use respiratory protection consistent with airborne infection control precautions, regardless of presumptive immunity status.55

Serologic screening of HCP during an outbreak to determine measles immunity prior to vaccination is not recommended, because preventing measles transmission requires the rapid vaccination of HCP without presumptive evidence of immunity, which can be impeded by the need to screen, wait for results, and then contact and vaccinate susceptible persons. Results from serological testing, if performed, can inform on need for the second MMR vaccine dose.

Hospitalized patient contacts of a case who do not have presumptive evidence of measles immunity should be vaccinated or offered immune globulin, and placed on airborne precautions until 21 days after their last exposure to the case-patient or four days after the onset of rash should they develop measles.60 If immune globulin is administered to an exposed person, observations should continue for signs and symptoms of measles for 28 days after exposure since immune globulin may prolong the incubation period.55

Healthcare facilities can also prepare for measles cases and outbreaks in the following ways:

• Develop a protocol for measles evaluation and testing in the event that a known measles contact requires evaluation and testing at a clinical site (e.g., avoiding exposure in the waiting room to other vulnerable populations)
• Be prepared to identify all patients, visitors, and staff who may have been exposed to a measles case, should a case be confirmed to have visited the facility during their infectious period
• Educate healthcare personnel on triage and management of measles cases, to ensure early isolation of suspect measles cases
• Education healthcare personnel on how to report suspect and confirmed measles cases to jurisdictional public health authorities
• Consider targeted outreach to healthcare settings in proximity to areas of lower measles vaccination rates
• Establish protocols for measles testing (e.g., routine use of PCR), including routing specimens to public health laboratories
• Establish protocols for use of post-exposure prophylaxis in response to measles exposures in healthcare settings

For additional details, including patient isolation and transport and management of visitor access to healthcare facilities please see: Interim Measles Infection Control Guidance.

Additional information

Because investigating an outbreak requires many person-days of work, personnel are frequently transferred to the activity from other areas in the health department or from other health departments and may only be involved in outbreak investigation for a few days before they are replaced by others. This turnover in personnel can cause problems unless activities are organized so that the status of the investigation is always documented. Some practical suggestions for organizing this activity are listed here.

• Identify a team leader for case investigators so that at least one person knows about all the new cases called in that day and what still needs to be done. Daily briefings are a good way of keeping the whole staff informed of the status of the investigation.
• Use an electronic spreadsheet or other database to record all suspected cases as they are received. The person who receives the initial telephone call should attempt to obtain the information needed to fill in the line listing (see above: Reporting and Case Notification).
• Track the actions needed for each suspected case ("collect NP swab," "draw blood," "call pediatrician for vaccination history," "notify contacts").
• Establish protocols for control measures necessary for all likely situations (exposure in a childcare center, school, doctor's office, workplace) and clearly define who (local health officer, immunization program manager) will make the decision to proceed when a case investigator identifies a situation that might require major investments of health department resources (such as managing exposures and vaccinations in a school setting).

Acknowledgements

Prior versions of this chapter were authored by Paul A. Gastanaduy, Susan Redd, Nakia Clemmons, Carole Hickman, and Manisha Patel.

Authors and Suggested Citation

Thomas D. Filardo, MD; Adria Mathis, MSPH; Kelley Raines, MPH; Nina B. Masters, PhD; Ashrita Rau, MPH; Stephen N. Crooke, PhD; Paul Rota, PhD; David Sugerman, MD MPH.

Suggested citation:

Given the variations in the timing for when chapter updates are made, a Manual edition number is no longer used. Therefore, it is recommended that the date at the top right of the web page be used in references/citations.

Content source:
National Center for Immunization and Respiratory Diseases