Disclosures: Hayley Gans, MD Nothing to disclose. Yvonne A Maldonado, MD Nothing to disclose. Martin S Hirsch, MD Nothing to disclose. Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: Pfizer [vaccine (PCV13)]; Forest Lab [antibiotic (Ceftaroline)]; Optimer [antibiotic (fidaxomicin)]. Consultant/Advisory Boards: Pfizer [vaccine (PCV13)]. Elinor L Baron, MD, DTMH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
INTRODUCTION — Measles is a highly contagious viral infection characterized by fever and exanthem . Infection with measles is highly preventable by existing vaccines.
Control measures for the prevention and spread of measles and treatment modalities for the virus will be reviewed here. The epidemiology, aims for global eradication, clinical manifestations, and diagnosis are discussed separately. (See "Epidemiology and transmission of measles" and "Clinical manifestations and diagnosis of measles".)
PREVENTION OF MEASLES
Vaccination — Measles vaccination has markedly reduced the incidence of measles virus infection and is one of the most successful global public health interventions; it prevents millions of deaths annually, primarily among infants and young children [2,3].
Measles vaccination has led to interruption of measles virus transmission in the developed world and affords protection to unvaccinated individuals via herd immunity. Measles vaccination is also important for preventing severe sequelae of measles virus infection as well as immunosuppression, which is associated with secondary infection [4,5]. (See "Clinical manifestations and diagnosis of measles".)
In low-incidence countries, measles continue to occur via importation of virus by travelers. The majority of measles cases (>80 percent) occur among unvaccinated individuals [6,7]. For this reason, maintenance of herd immunity is critical; otherwise, a single imported case can result in large measles outbreaks. To disrupt broad transmission, herd immunity must be maintained above 85 to 95 percent . Two doses of measles vaccine are required in children for ongoing elimination and to maintain herd immunity . (See "Epidemiology and transmission of measles".)
Factors to be considered when determining the need for measles vaccination include the age of the recipient, the date of administration of the first dose of vaccine (in considering the second dose), local measles epidemiology, the type of measles vaccine administered previously, contraindications to vaccination, travel plans, and evidence of prior measles infection. Comprehensive vaccination strategies should also include immunizations in foreign-born adults; in one study of immigrants and refugees to Canada, 36 percent of participants were nonimmune to at least one of three vaccine-preventable diseases (eg, measles, mumps, or rubella) . (See "Epidemiology and transmission of measles".)
Issues related to measles-mumps-rubella vaccination in infants, children, and adolescents are discussed in detail separately. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents".)
Types of vaccines — The only vaccine virus strain currently in use in the United States (US) is the Enders-Edmonston strain; it is a live attenuated vaccine licensed for use in the United States in 1968. In the United States, it is available in combination as a measles-mumps-rubella (MMR) vaccine  and as the quadrivalent measles-mumps-rubella-varicella (MMRV) vaccine. Several other vaccines, also derived from attenuated measles virus strains, are in use in other parts of the world.
MMRV vaccine was approved by the US Food and Drug Administration (FDA) in 2005 for individuals aged 12 months to 12 years. MMRV has comparable immunogenicity to simultaneous MMR and varicella vaccination . In postlicensure studies, MMRV was associated with a small increased risk for febrile seizures; this risk was present at the typical age of receipt for the first dose of vaccine but not at the age of receipt for the second dose . The Advisory Committee on Immunization Practices (ACIP) reviewed the risks and benefits of MMRV compared with simultaneous MMR and varicella vaccine and issued recommendations for use as follows [11,12]:
●For the first dose of measles, mumps, rubella, and varicella vaccines at age 12 to 47 months, either separate MMR and varicella vaccines or MMRV vaccine may be used. Providers considering administration of MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine, the Centers for Disease Control and Prevention (CDC) recommends that separate MMR and varicella vaccines be administered for the first dose in this age group.
●For the second dose of measles, mumps, rubella, and varicella vaccines at any age (15 months to 12 years) and for the first dose at age ≥48 months, use of MMRV vaccine generally is preferred over separate injections of its equivalent component vaccines (ie, MMR vaccine and varicella vaccine). Considerations should include provider assessment, patient preference, and the potential for adverse events. Provider assessment denotes consideration of "the number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, and storage and cost considerations."
Measles vaccine strains previously employed in the United States include an inactivated Edmonston B vaccine (distributed from 1963 to 1967), a live attenuated Edmonston B vaccine (distributed from 1963 to 1975), and a live attenuated Schwarz vaccine (introduced in 1965). The inactivated Edmonston B vaccine strain was associated with severe atypical measles in those exposed to live measles after vaccination (see "Clinical manifestations and diagnosis of measles", section on 'Atypical measles').
An aerosolized vaccine against measles was immunogenic but inferior to the subcutaneous vaccine with respect to seropositivity rate (85.4 versus 94.6 percent at day 91) among 1560 children 9 to 11.9 months of age in India .
Vaccine effectiveness — Measles vaccination usually leads to long-term immunity. In the United States, measles antibodies develop in 96 percent of individuals vaccinated at age 12 months and in 98 percent of individuals vaccinated at age 15 months [14,15]. For the small percentage of nonresponders to the first vaccine dose, a second dose will result in seroconversion in 90 percent , resulting in 99 percent immunity among individuals who have received two doses of measles vaccine . Thus, the second vaccine dose is not a booster dose but serves to provide immunity among nonresponders.
Waning of immunity after vaccination, known as secondary vaccine failure, is relatively rare . Most individuals with low antibody titers demonstrate an anamnestic immune response upon revaccination, indicating that they are probably still immune despite low titers .
In many countries outside the United States, measles vaccination is administered at age nine months in order to provide earlier immunity among children more likely to be exposed to measles at young ages. The effectiveness of vaccination at this age is approximately 85 percent [18-23].
Low-prevalence settings — For prevention of measles infection in the United States, we agree with the ACIP, which recommends one dose of MMR at age 12 to 15 months followed by a second dose administered no sooner than 28 days later (figure 1) [11,12,14]. The American Academy of Pediatrics (AAP), the American Academy of Family Physicians (AAFP), and the ACIP all recommend that the second dose of vaccine be given prior to school entry (ages four to six years). (See "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'Measles, mumps, and rubella infections'.)
In the United States, high-risk regions are defined by the ACIP as counties with a large inner-city population, counties with a recent measles outbreak among unvaccinated preschool children, and counties with more than five cases of measles among preschool-aged children during the preceding five years . In such regions, the first dose of measles vaccine should be given at age 12 months rather than 15 months. The benefit of preventing measles cases among children aged 12 to 15 months outweighs the risk of slightly reduced vaccine efficacy at this age. Individuals with inadequate response to the first vaccination are likely to develop sufficient immunity with the second vaccination.
International travelers aged 6 to 11 months should have one MMR dose before departure. MMRV is not licensed for children <12 months of age and should not be used in this setting. Children who receive a dose of measles vaccine before their first birthday should be revaccinated with two doses of MMR vaccine; one vaccination should occur when the child is aged 12 to 15 months and at least 28 days after the initial measles immunization (12 months if the child remains in a high-risk area), and another vaccination should occur at school entry (4 to 6 years old). Other international travelers should have documentation of two doses of live measles vaccine.
It is safe to administer most vaccines with MMR during the same visit, including :
●Diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) or diphtheria toxoid/tetanus toxoid/whole-cell pertussis vaccine (DTP)
●Haemophilus influenzae type b vaccine (Hib)
●Inactivated polio vaccine (IPV) or oral polio vaccine (OPV) – Current recommendations are to use IPV instead of OPV in most countries .
Live measles and yellow fever vaccines can be administered simultaneously at separate anatomical sites in separate syringes. Limited data exist regarding interactions between MMR and Japanese encephalitis vaccine, meningococcal vaccine, or typhoid vaccine, but a significant interaction is not expected to occur .
High-prevalence settings — In settings with high prevalence of measles, the World Health Organization (WHO) recommends that the first dose of MMR be administered at age 9 months rather than 12 months . Schedules for individual countries are available through the World Health Organization.
Children are at risk for measles following clearance of protective transplacentally acquired maternal antibodies [26-29]. The degree of infant protection depends on maternal antibody titer [30-32]. Lower levels of measles virus antibodies have been observed among vaccinated mothers than mothers with immunity following natural infection . Maternal antibody levels correlate with neonatal antibody levels at birth (r = 0.93), and the median time to loss of immunity is shorter for infants of vaccinated women than for infants of naturally immune women (0.97 months versus 3.78 months, respectively). At six months of age, measles antibody titers are undetectable in more than 99 percent of neonates born to vaccinated mothers and 95 percent of neonates born to naturally immune mothers . This suggests that by age six months, children are at risk for becoming infected with measles virus and that the number of children at risk may grow as mothers with vaccine-induced measles immunity replaces mothers with natural immunity .
In addition, the risk of acquiring measles virus infection prior to measles vaccination (administered at 9 to 15 months of age) is higher among infants born to HIV-infected women than those born to HIV-uninfected women . In a study of 747 paired maternal cord serum samples (91 from HIV-infected and 656 from HIV-uninfected mothers), infants born to HIV-infected mothers had lower measles virus antibody titers at birth and were more likely to be uninfected at 9 months of age; infected infants had titers that were 35 percent lower than titers in infants born to HIV-uninfected mothers .
The above observations have led to the suggestion that an early two-dose vaccination program may be beneficial [33-35]. An interim analysis of a randomized trial of measles vaccine at age 4.5 months found that, in a coincidental outbreak, the monthly incidence of measles was 0.7 percent in the early vaccination group versus 3.1 percent in the control group . The investigators cautioned that the results likely only applied to the measles vaccine used in the study (Edmonston-Zagreb).
Infants vaccinated at a younger age are less likely to develop seroprotective antibodies following measles vaccine. The 2009 WHO vaccination guidelines estimate that, at age 8 to 9 months, a median 89 percent of infants seroconvert after one dose of measles vaccine (interquartile range [IQR]: 82 to 95 percent), and, at age 11 to 12 months, a median 99 percent of infants seroconvert (IQR: 93 to 100 percent). A review of measles vaccine effectiveness noted that the median effectiveness for a single dose of measles vaccine was higher when given at age >12 months than at age 9 to 11 months, 92.5 percent (IQR: 85 to 97 percent) versus 84 percent (IQR: 72 to 95 percent), respectively . However, T cell immunity appears to be spared even in infants as young as six months of age .
Among HIV-infected children, rapid waning of measles virus antibodies suggests that more than two doses of measles vaccine are needed, particularly after immune reconstitution . In a prospective study including 696 children, antibody titers 27 months after vaccination were detectable less frequently among HIV-infected children than HIV-uninfected children (50 percent versus 89 percent, respectively) . In another study among adolescents and young adults, higher measles antibody titers were observed if initial vaccination was administered when infected children were receiving antiretroviral therapy. Responses were dependent on time since last vaccine, suggesting waning immunity over time .
Issues related to measles immunization in HIV-infected patients are discussed separately. (See "Immunizations in HIV-infected patients", section on 'Measles, mumps, and rubella vaccine'.)
Adults at increased risk for exposure to measles include individuals attending colleges and other post–high school educational institutions, those working in medical facilities, and international travelers .
Previous vaccination with live attenuated Edmonston B measles vaccine (1963 to 1975) is considered an effective first dose of vaccine if given at age 12 months or older. If indicated, a second dose of MMR vaccine should be administered.
All other individuals are considered unvaccinated, including:
●Those vaccinated with a further attenuated strain (Schwarz or Moraten), especially if coadministered with immune globulin
●Those vaccinated with an unknown strain, with or without immune globulin coadministration
●Those vaccinated with inactivated measles vaccine or vaccine of unknown type between 1963 and 1967
These individuals should receive two doses of live vaccine separated by at least 28 days. Those who received inactivated virus vaccine followed within three months by live virus vaccine should also be revaccinated with two doses of live virus vaccine separated by at least 28 days.
Issues related to measles immunization in healthcare workers (including those born before 1957) are discussed below. (See 'Healthcare personnel' below.)
Issues related to measles immunization in HIV-infected patients are discussed separately. (See "Immunizations in HIV-infected patients", section on 'Measles, mumps, and rubella vaccine'.)
Contraindications — Contraindications to measles vaccination are summarized below. In the setting of measles exposure, individuals with contraindications to vaccination should receive immune globulin . (See 'Immune globulin' below.)
●Pregnancy – Measles disease can be more severe in pregnancy (see "Clinical manifestations and diagnosis of measles"), but because of a theoretical risk of birth defects among children born to mothers who receive live viral vaccine during pregnancy, the vaccine is considered contraindicated in pregnant women. Women of childbearing age should be counseled to avoid pregnancy for 30 days after vaccination ; however, all pregnant women without measles immunity should receive a dose of MMR postpartum. Children residing in a home with pregnant individuals should receive MMR vaccine on schedule . (See "Immunizations during pregnancy", section on 'Measles, mumps, rubella'.)
●Immunosuppression – Live measles vaccine or MMR should be used with caution in severely immunocompromised individuals. Issues related to immunizations in patients with immune suppression due to various causes are discussed separately. (See "Immunizations in HIV-infected patients", section on 'Measles, mumps, and rubella vaccine' and "Immunizations in patients with cancer", section on 'Measles, mumps, and rubella vaccines' and "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Measles, mumps, and rubella' and "Immunizations in solid organ transplant candidates and recipients", section on 'Measles, mumps, and rubella'.)
MMR or live measles virus vaccination should be postponed in patients receiving steroids (prednisone >2 mg/kg or 20 mg daily or every other day for more than 14 days). Vaccine should not be administered until at least one month after the cessation of steroid treatment.
Close contacts of immunocompromised patients should receive routine measles vaccination; secondary transmission associated with vaccination has not been reported .
●Allergy – A history of anaphylaxis after ingestion of gelatin is associated with an increased risk of anaphylaxis with MMR or MMRV . This history warrants a skin test for gelatin allergy.
A history of anaphylactic reaction to neomycin is a contraindication for receipt of MMR or MMRV. A history of contact dermatitis to neomycin (which reflects a delayed or cell-mediated immune response) is not a contraindication to vaccination.
A history of severe allergic reaction to any component of the vaccine is a contraindication for receipt of MMR or MMRV.
A history of anaphylaxis after egg ingestion is not a contraindication to measles immunization. (See "Allergic reactions to vaccines".)
Precautions — Precautions for MMR and MMRV vaccination include:
●Recent receipt of blood products or immune globulin – Vaccine efficacy is diminished significantly by prior passive administration of antibody. Vaccination should be delayed for 3 to 11 months after immunoglobulin administration (table 1) [14,41].
●Concurrent illness – Vaccination should be delayed in persons with moderate to severe illness with or without fever, including untreated active tuberculosis, until resolution of the acute phase of the illness as long as the vaccine is not being administered for an exposure . However, mild febrile or nonfebrile illnesses do not mandate delay of vaccination.
●History of thrombocytopenia – Individuals with a history of thrombocytopenia are at increased risk of developing significant thrombocytopenia after MMR vaccination . However, the benefits of primary vaccination usually outweigh the risks. It may be prudent to avoid a second dose of MMR in individuals with history of thrombocytopenia within six weeks of initial vaccination .
●Tuberculin testing – MMR vaccine may result in a temporary reduction in tuberculin skin sensitivity . Tuberculin testing should be performed prior to, simultaneously with, or at least four to six weeks after vaccination. The effect of live virus vaccination on interferon-gamma release assay (IGRA) is uncertain .
●Personal or family history of seizures – A personal or family (sibling or parent) history of seizures is a precaution for the first dose of MMRV but not MMR vaccination . In postlicensure studies, MMRV was associated with a small increased risk for febrile seizures; this risk was present at the typical age of receipt for the first dose of vaccine but not at the age of receipt for the second dose . There is no known link between varicella vaccine and febrile seizures; the reason for this association is uncertain . Individuals with a personal or family history of seizures should be vaccinated with MMR vaccine for the first dose of measles vaccine.
Adverse events — A variety of adverse reactions have been reported following measles-mumps-rubella vaccine administration . Transient fever (39.4°C or higher occurring one to two weeks after vaccination) develops in 5 to 15 percent of vaccinees. Transient rash occurs in approximately 5 percent. These individuals are not thought to be contagious. Transient lymphadenopathy occurs in 5 percent of children and 20 percent of adults . Most hypersensitivity reactions to the vaccine are minor. Anaphylaxis can occur but is extremely rare. Epinephrine should be available for use at any site that administers the vaccine.
Thrombocytopenia has been observed in prospective studies (1 case in 25,000 to 40,000 vaccine doses) . In general, it is transient and occurs within two months of the receipt of vaccine, most commonly at two to three weeks. The risk may be higher in individuals who experienced thrombocytopenia following previous vaccination with MMR. (See 'Precautions' above.)
Administration of MMR has been associated with febrile seizures, arthralgias or arthritis, anaphylaxis, and measles inclusion body encephalitis in immunodeficient individuals . The incidence of vaccine-associated seizures has been estimated to be 1 in 3000 MMR doses  but is increased in vaccinees with a history of seizures or with a family history in first-degree relatives. Most are simple febrile seizures. In most cases, the benefits of vaccination outweigh the risk of seizures. The incidence of anaphylaxis is unknown but is estimated by the CDC to be less than one per every one million MMR doses distributed .
Lack of association with autism — Numerous studies have failed to demonstrate any association between MMR vaccination and autism. This is discussed further separately. (See "Autism and chronic disease: No evidence for vaccines as a contributing factor".)
Evidence of measles immunity — Evidence for measles immunity is important in order to determine if subsequent vaccination is needed. The criteria below are accepted by the ACIP as presumptive evidence of measles immunity. Nonetheless, transmission of infection can occur even among individuals who meet criteria for presumptive immunity.
Clinical diagnosis of measles documented by a physician is not considered an acceptable criterion for evidence of measles immunity [41,47].
Documentation of vaccination — Written documentation of vaccination is required; a self-report of measles vaccination is not adequate. The definitions of adequate measles vaccination differ by group.
●Preschool-aged children: One dose of vaccine administered on or after the first birthday.
●School-aged children (kindergarten through twelfth grade): Two doses of vaccine administered after age 12 months and separated by at least 28 days. The American Academy of Pediatrics, the American Academy of Family Physicians, and the Advisory Committee on Immunization Practices all recommend that the second dose of vaccine be given prior to school entry (ages four to six years).
●Adults at high risk, including students at post–high school educational institutions (colleges, universities, vocational schools, and technical schools), healthcare personnel (including volunteers, students, nonmedical workers, part-time workers, and persons without patient care responsibilities), and international travelers: Two doses of vaccine separated by at least 28 days.
●International travelers aged 6 to 11 months: One dose of vaccine before departure. Children who receive a dose of measles vaccine before their first birthday should be revaccinated with two doses of MMR vaccine; one vaccination should occur when the child is aged 12 to 15 months and at least 28 days after the initial measles immunization (12 months if the child remains in a high-risk area), and another vaccination should occur at school entry (4 to 6 years old) . Other international travelers should have documentation of two doses of live measles vaccine.
Laboratory evidence of immunity — Anti-measles virus antibody unequivocally detected by any serologic test is considered evidence for immunity. A negative serologic test should prompt vaccination except in individuals with contraindications. (See 'Contraindications' above.)
Individuals lacking serologic evidence of immunity are at risk of acquiring disease. It is rare for immunocompetent individuals to lack laboratory evidence of immunity after two doses of MMR; in such cases, a third dose of MMR should be administered.
Screening in non-outbreak situations is most effective when follow-up is assured (eg, hiring of new healthcare workers). If follow-up for reporting results and administering vaccine is not possible, screening should not be performed. Screening is not advised during an outbreak situation; vaccination should be administered.
Laboratory confirmation of disease — The diagnosis of measles is discussed separately. (See "Clinical manifestations and diagnosis of measles", section on 'Diagnosis'.)
Birth before 1957 — Most individuals born before 1957 have had natural measles infection given the widespread measles epidemics in the United States before the introduction of measles vaccine.
Issues related to vaccination of healthcare personnel born before 1957 are discussed below. (See 'Healthcare facilities' below.)
Controlling spread — A measles outbreak has been defined by the CDC as "a chain of transmission with three or more confirmed cases linked in time and space" . Control of outbreaks is of paramount importance in the prevention of measles. Suspected cases of measles should be reported immediately to the local or the state health department, and all such reports should be investigated promptly. Control measures should not be delayed while waiting for laboratory confirmation of the diagnosis . (See 'Outbreak control measures' below.)
Postexposure prophylaxis — Postexposure prophylaxis for susceptible individuals exposed to measles consists of vaccination within 72 hours of exposure in the absence of a contraindication. If more than 72 hours but fewer than 6 days have elapsed since exposure, immune globulin may prevent or modify measles infection in susceptible individuals.
Vaccination — MMR vaccination can provide some protection or modify the clinical course of measles if administered within 72 hours of measles exposure . For vaccine-eligible individuals aged ≥12 months who have been exposed to measles, MMR vaccine should be administered unless there is a contraindication, including individuals who have only received one previous vaccine dose. Administration of vaccine is preferable to administration of immune globulin since vaccination provides active, long-lasting immunity against measles . In one of the largest outbreaks in Australia, postexposure MMR vaccination was 100 percent effective and immunoglobulin 74 percent with the only cases developing among those who received immunoglobulin on the seventh day after exposure .
Infants aged 6 to 11 months are at greater risk for severe disease. Infants with measles virus exposure may receive vaccination, although they must undergo repeat immunization at age 12 to 15 months and again prior to school entry. When infants receiving an early measles vaccine dose between 6 and 11 months followed by a dose after 12 months were studied during and after a measles epidemic, the early two-dose strategy was 99.5 percent effective against measles disease and antibody titers measured at 4 to 6 years of age were comparable to titers measured in children who had received one measles dose at 12 to 18 months . For infants exposed to measles virus within the household, immunoglobulin administration may be preferable since the risk for acquiring infection in this setting is higher than for other types of exposure .
The evidence for efficacy of MMR vaccine administered as postexposure prophylaxis is limited and mixed [51-53]. Prophylactic postexposure vaccination may provide some protection against infection or modify the clinical course of disease if administered within 72 hours of initial measles exposure in settings of limited contact such as schools and daycare centers . The efficacy is likely to be diminished in settings with intense, prolonged contact, such as households, because individuals in these settings are frequently exposed for prolonged duration during the prodromal period when the index patient is infectious. If, despite vaccination, exposure results in measles infection, there is no evidence that receipt of MMR vaccine during the presymptomatic or prodromal stage of illness increases the risk for vaccine-associated adverse events .
Immune globulin — Immune globulin can prevent or diminish the severity of measles if administered to nonimmune individuals within six days of exposure [14,54]. Administration of immune globulin is appropriate for exposed individuals with increased risk of measles complications as summarized below .
For exposed individuals not belonging to these groups, the administration of live measles vaccine within 72 hours of the exposure is preferable to immune serum globulin administration . Immune globulin is not indicated for individuals who have received one dose of measles-containing vaccine at age ≥12 months in the absence of immunosuppression.
Any nonimmune individual exposed to measles who received immune globulin should subsequently receive MMR vaccine (no earlier than six months after intramuscular immune globulin [IGIM] or eight months after intravenous immune globulin [IVIG]), provided the individual is then ≥12 months of age and the vaccine is not otherwise contraindicated.
Administration of immune globulin should not be used for outbreak control .
Infants aged <12 months — Infants are at increased risk for severe measles and complications and are susceptible to measles if mothers are nonimmune or maternal antibodies have waned. Therefore, administration of immune globulin administered intramuscularly (IGIM 0.5 mL/kg; maximum dose 15 mL) is appropriate for exposed infants aged <12 months. Infants aged 6 to 11 months may receive MMR vaccine in place of immune globulin if administered within 72 hours of exposure.
Pregnant women without evidence of immunity — Pregnant women may be at increased risk for severe measles and complications. Therefore, administration of intravenous immune globulin (IVIG 400 mg/kg) is appropriate for pregnant women without evidence of measles immunity who have been exposed to measles.
Immunocompromised patients — Immunocompromised patients exposed to measles should receive postexposure prophylaxis with IVIG (400 mg/kg) regardless of immunologic or vaccination status. Such patients include individuals with severe immunodeficiency, bone marrow transplant recipients until at least 12 months after completing all immunosuppressive treatment (or longer in patients with graft-versus-host disease), patients on treatment for acute lymphoblastic leukemia until at least six months after completion of immunosuppressive chemotherapy, patients with HIV infection and CD4 percent <15 percent (all ages) or CD4 count <200 lymphocytes/mm³ (age >5 years), and patients who have not received MMR vaccine since receiving effective antiretroviral therapy.
Outbreak control measures — A measles outbreak has been defined by the CDC as "a chain of transmission with three or more confirmed cases linked in time and space" . Prevention of spread in the setting of an outbreak depends upon prompt administration of vaccine to all susceptible persons. Criteria for evidence of measles immunity are summarized above. (See 'Evidence of measles immunity' above.)
Individuals unable to produce documentation of measles immunity should be excluded from the outbreak setting until they have complied with vaccination requirements. Those who are exempt from vaccination for medical, religious, or other reasons should be excluded from the outbreak setting for a minimum of three weeks after the onset of rash in the last measles case. Quarantine measures are not otherwise routinely recommended in outbreak control .
Case definitions — Several case definitions have been established to standardize the approach to measles outbreaks [9,14].
●Suspected case – A suspected case is defined as a febrile illness accompanied by rash.
●Clinical case – A clinical case is defined as an illness characterized by cough, coryza, or conjunctivitis, a generalized rash lasting for more than three days, and a temperature >38.3°C (>101°F).
●Probable case – A probable case meets the clinical case definition but is not linked epidemiologically to a confirmed case and lacks serologic or virologic proof of disease.
●Confirmed case – A confirmed case meets the laboratory criteria for measles (independent of clinical features) or meets the clinical case definition and is epidemiologically linked to a confirmed case.
Healthcare facilities — Between 2001 and 2014, 78 reported measles cases resulted from transmission in US healthcare facilities, and 29 healthcare personnel were infected from occupational exposure .
Employees without evidence of measles immunity should be vaccinated. Susceptible healthcare workers with measles virus exposure should be vaccinated within 72 hours of exposure. All exposed individuals without evidence of immunity should be excluded from the workplace from day 5 through day 21 after exposure. If the case is confirmed, even those who were vaccinated within 72 hours should be excluded . (See "Epidemiology and transmission of measles", section on 'Transmission'.)
Acquisition and transmission of measles virus by hospital workers born before 1957 with no serologic evidence of measles immunity in the healthcare setting has been described . Given the risk of occupational exposure to measles virus and the risk that healthcare workers with measles may transmit infection to others in a healthcare setting, we agree with the CDC and ACIP, which state vaccination (two doses of MMR) is warranted for these individuals [45,59].
Infection control — Strict isolation techniques decrease transmission rates in outbreak situations .
In the outpatient setting, patients with febrile rash illness should be escorted to a separate waiting area or placed immediately in a private room, preferably at negative pressure relative to other patient care areas. Both patients and staff should wear appropriate masks/respirators (masks for patients to prevent generation of droplets, and respirators for staff to filter airborne particles). If not admitted, patients should be told to remain in isolation at home through four days after rash onset. Measles virus can remain suspended in the air for up to two hours; therefore the room occupied by a suspect case should not be used for two hours after the patient's departure.
In the inpatient setting, airborne transmission precautions are indicated for four days after the onset of rash in otherwise healthy patients and for the duration of illness in immunocompromised patients . (See "General principles of infection control", section on 'Airborne precautions'.)
Susceptible individuals should not enter the room of patients with suspected or confirmed measles. Exposed susceptible individuals should be excluded from work from day 5 through day 21 after exposure. If the case is confirmed, even those who were vaccinated within 72 hours should be excluded.
TREATMENT OF MEASLES — The treatment of measles is supportive; there is no specific antiviral therapy approved for treatment of measles. There is a role for vitamin A in certain settings, discussed below [62,63]. The World Health Organization (WHO) has published a comprehensive guide to the treatment of measles . Supportive therapy includes antipyretics, fluids, and treatment of bacterial superinfections, such as bacterial pneumonia and otitis. Treatment of other complications, such as seizures and respiratory failure, may also be necessary. (See "Clinical manifestations and diagnosis of measles".)
Antibiotic prophylaxis during measles epidemics may prevent complications; further study is needed [65,66].
Vitamin A — Vitamin A deficiency contributes to delayed recovery and to the high rate of post-measles complications. In addition, measles infection may precipitate acute vitamin A deficiency and xerophthalmia .
Administration of vitamin A to children with measles is associated with decreased morbidity and mortality [68-70].
Low serum concentrations of vitamin A have been observed among children in the United States (US), and lower concentrations have been observed in children with more severe illness. The use of vitamin A for treatment of measles in developed countries has not been evaluated in a clinical trial.
The WHO recommends that vitamin A be administered to all children with acute measles [67,71]. Even in countries where measles is not usually severe, vitamin A should be given to all cases of severe measles (such as those who are hospitalized) .
Vitamin A for treatment of measles is administered once daily for two days, at the following doses:
●Infants <6 months of age: 50,000 international units
●Infants 6 to 11 months of age: 100,000 international units
●Children ≥12 months: 200,000 international units
For children with clinical signs and symptoms of vitamin A deficiency (such as Bitot's spots), a third dose of vitamin A should be administered four to six weeks later.
Ribavirin — Measles virus is susceptible to ribavirin in vitro; there have been no randomized controlled trials to assess its clinical benefit. Data on use of ribavirin are limited:
●In a randomized trial including 100 children with measles treated with ribavirin or supportive care, those who received ribavirin had a shorter duration of fever, constitutional symptoms, and length of hospitalization . No complications were observed in the treatment group, while several severe complications occurred in the untreated group.
●During a measles outbreak on a pediatric oncology ward, ribavirin given with vitamin A resulted in recovery in 13 of 15 cases; one of the deaths was in a child with delayed initiation of ribavirin .
●Another case series reported a favorable outcome in five of six adults with severe measles pneumonitis who received intravenous ribavirin. Those who recovered received the drug on day 2 to day 5 of illness; the patient who died of progressive respiratory failure received the drug on day 22 of infection .
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient information: Measles (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Measles is a highly contagious viral infection characterized by fever and exanthem. Prevention depends upon vaccination of all susceptible individuals. Maintenance of herd immunity is important even in countries with a low incidence of measles. (See 'Vaccination' above.)
●Susceptible individuals are those without evidence of measles immunity, which includes one of the following: documentation of vaccination, laboratory evidence of immunity, laboratory confirmation of disease, or birth before the year 1957. (See 'Evidence of measles immunity' above.)
●In the United States (US), we follow recommendations issued by the Advisory Committee on Immunization Practices (ACIP), as follows: one dose of measles-mumps-rubella (MMR) vaccine at age 12 to 15 months, followed by a second dose administered no sooner than 28 days later. The second dose of vaccine is generally administered prior to school entry (ages four to six years). (See 'Low-prevalence settings' above.)
●Some nations with high measles prevalence use the World Health Organization (WHO) strategy of administering the first dose of MMR at age 9 months rather than 12 months. Schedules for individual countries are available through the World Health Organization. (See 'High-prevalence settings' above.)
●Contraindications to measles vaccination include pregnancy, immunosuppression, and allergy. (See 'Contraindications' above.)
●Postexposure prophylaxis for susceptible individuals exposed to measles virus consists of vaccination within 72 hours of exposure (in the absence of a contraindication). If more than 72 hours but less than 6 days have elapsed since exposure, intramuscular immune globulin may prevent or modify measles infection in susceptible individuals. (See 'Postexposure prophylaxis' above.)
●Administration of immune globulin is appropriate for exposed individuals with increased risk of measles complications, including infants <12 months, pregnant women without evidence of immunity, and immunocompromised patients. (See 'Immune globulin' above.)
●The treatment of measles is largely supportive. Supportive therapy includes antipyretics, fluids, and treatment of bacterial superinfections and other complications. (See 'Treatment of measles' above.)
●Vitamin A may be beneficial in the setting of measles infection; data are limited. We suggest administering vitamin A to children with acute measles; even in countries where measles is not usually severe, vitamin A should be given to all cases of severe measles. (Grade 2B). (See 'Vitamin A' above and 'Ribavirin' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Jorge L Barinaga, MD, MS, and Paul R Skolnik, MD, FACP, FIDSA, who contributed to an earlier version of this topic review.
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