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 [S. pneumoniae (PCV13, Linezolid)]; Cubist [S. aureus (Tedizolid)]; Forest Lab [Osteomyelitis (Ceftaroline)]. Consultant/Advisory Boards: Pfizer [S. pneumoniae (PCV13, Linezolid); S. aureus (vaccine development)]; Theravance [S. aureus (Telavancin)]. 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 illness characterized by fever, malaise, rash, cough, coryza, and conjunctivitis . Measles has been targeted for eradication given the favorable biologic characteristic that humans are the only reservoir ; however, due to social and political factors and high transmissibility, elimination has been achieved in very few areas of the world [3,4].
The epidemiology and transmission of measles will be reviewed here. The clinical manifestations, diagnosis, prevention, and treatment are discussed separately. (See "Clinical manifestations and diagnosis of measles" and "Prevention and treatment of measles".)
EPIDEMIOLOGY — Measles occurs worldwide. Control efforts have substantially altered the global distribution ; measles incidence has decreased substantially in regions where vaccination has been instituted, and, as a result, measles occurs predominantly in areas with low vaccination rates, particularly in the developing world .
During the prevaccine era, more than 90 percent of children acquired measles by age 15 [7-9]. Following implementation of routine childhood vaccination in the United States at age 12 to 15 months, the age of peak measles incidence during epidemics in the United States shifted to <12 months. This susceptibility approximates the time at which transplacentally acquired maternal antibodies are no longer present if the mother has vaccine-induced immunity [10-12].
Worldwide, measles is a significant cause of morbidity and mortality. Precise incidence estimates are difficult to obtain because of heterogeneous surveillance systems and probable underreporting . Before the introduction of the measles vaccine, over two million deaths occurred annually, the majority in children <5 years of age .
Availability of measles vaccination beginning in the 1960s immediately impacted disease incidence and mortality rates. Vaccination rates vary worldwide; in 2013, there were an estimated 145,700 deaths reported, predominantly in the developing world . Measles is the fifth most common cause of death in children <5 years of age [13,16,17].
TRANSMISSION — Measles is highly contagious; the attack rate in a susceptible individual exposed to measles is 90 percent [18,19]. Transmission occurs via person-to-person contact as well as airborne spread. Infectious droplets from the respiratory secretions of a patient with measles can remain airborne for up to two hours [19,20]. Therefore, the illness may be transmitted in public spaces, even in the absence of person-to-person contact. Measles transmission between airplane passengers in airports and during flight has been described [21-23], and large outbreaks can occur in areas of crowding such as schools and densely populated communities.
The incubation period for measles is 6 to 19 days (median 13 days) . Subclinical illness is unusual. The period of contagiousness is estimated to be from five days before the appearance of rash to four days afterward. The period of maximum contagiousness is thought to be during the late prodrome phase, when the patient is febrile and has respiratory symptoms. Patients with measles-associated subacute sclerosing panencephalitis are not contagious . (See "Clinical manifestations and diagnosis of measles".)
In temperate areas, the peak incidence of measles occurs in the late winter and early spring. However, cases occur throughout the year and, in some regions, no seasonal incidence is apparent.
INDIVIDUALS AT RISK — Individuals at risk for measles include children too young to be vaccinated, those who have not been vaccinated for medical or other reasons, those who have not received a second dose of measles vaccine, and those for whom the vaccine failed to elicit a protective immune response (a very small fraction of those immunized with two dose of vaccine).
Travel to areas where measles is endemic or contact with ill persons arriving from these countries increases the risk of exposure to measles .
ROLE OF PROTECTIVE IMMUNITY — Natural measles infection is thought to confer lifelong immunity. Immunity due to measles vaccination is also highly protective against clinical infection. During an outbreak in the Netherlands, for example, unvaccinated individuals were 224 times more likely to become infected compared with vaccinated individuals .
Children of mothers vaccinated against measles have lower concentrations of transplacentally acquired maternal antibodies to measles (and therefore lose protection afforded by maternal antibodies at an earlier age) than children born to mothers with immunity acquired from natural infection [12,28-30]. As a result, measles occurs more commonly among children <12 months in countries with high measles vaccine coverage [16,31]. (See "Prevention and treatment of measles", section on 'High-prevalence settings'.)
In developing countries, a younger age of measles infection has been noted among children born to HIV-infected mothers than children born to HIV-uninfected mothers. In this setting, the titer of transplacentally acquired measles antibody may be reduced. (See "Clinical manifestations and diagnosis of measles", section on 'Immunocompromised patients'.)
GLOBAL CONTROL — Ideally, immunization efforts should focus on control, followed by outbreak control, then elimination, and finally eradication . Population immunity of >95 percent is needed to stop ongoing transmission .
Tremendous progress has been made toward reducing the contribution of measles to childhood morbidity and mortality worldwide, largely through the commitment to achieve two-dose immunization strategies against measles in all regions of the world .
To reduce measles morbidity and mortality globally, in 2000 the World Health Assembly adopted the World Health Organization (WHO)/United Nations International Children's Emergency Fund (UNICEF) Global Immunization Vision and Strategy, which identified 47 priority countries to focus on measles mortality reduction efforts; jointly, these nations account for approximately 98 percent of measles deaths [16,35].
According to WHO and UNICEF estimates, global routine coverage with a first dose of measles vaccine increased between 2000 and 2013 from 72 to 85 percent, and 76 percent of countries included two doses of measles-containing vaccine regimens [14,34].
Initial efforts resulted in a 74 percent decline in measles mortality between 2000 and 2010, from 535,000 to 139,000 cases, which represented a 23 percent decline in under-five deaths worldwide between 1990 and 2008 . The majority of deaths occurred in Africa and India.
Continued efforts have been established through the Global Measles and Rubella Strategic Plan, with targets to reduce measles mortality by 95 percent of 2000 levels by 2015, by raising measles vaccination rates above 90 percent . Further information on measles control is available at the Measles and Rubella Initiative website and the WHO website.
The Americas — The WHO-designated Region of the Americas met its goal of eliminating endemic measles transmission in 2002 [17,37,38]. However, eradication has yet to be achieved because cases continue to occur due to measles virus importation, emphasizing the importance of maintaining routine vaccination . Between 1990 and 2008, measles cases in the region fell from 250,000 to 203 cases [37,39].
United States — In the decade before the measles vaccination program began, there were as many as 500,000 reported cases of measles per year in the United States; by one estimate, there may have been as many as four million cases per year . About 48,000 were hospitalized, 1000 were chronically disabled, and nearly 500 died.
The live attenuated measles vaccine was introduced in 1967 and, by 1985, had prevented about 52 million cases of measles, 5200 deaths, and 17,400 cases of permanent mental damage attributable to measles . Since that time, the number of cases has fallen by approximately 99 percent, and measles is no longer considered an endemic disease in the United States [41-43], with elimination of indigenous spread proclaimed in 2000 .
Between 1989 and 1991, the incidence of measles began to increase; a peak of 27,000 measles cases were reported, and there was a shift from the highest incidence affecting children 5 to 9 years of age (prior to immunization) to 45 percent of cases occurring in children <5 years of age . The United States Public Health Service responded by recommending a two-dose immunization schedule to immunize the 5 to 20 percent of individuals who had not responded to the first dose of the vaccine .
In 2002, measles was declared eliminated from the Americas . However, between 2001 and 2011, a median of 63 cases of measles (range 37 to 220) have occurred each year in the United States. Cases began to rise in 2008, and, since this time, there have been several outbreaks (three or more cases linked in time or place) [47,48]. Cases continue to occur in under- or unvaccinated populations associated with exposure to imported cases (figure 1). Among infected individuals who were United States residents, 85 percent were not vaccinated or had unknown vaccination status but were considered eligible for vaccination .
Measles imported by travelers to the United States is well described [50-54]; of 692 measles cases reported between 2001 and 2010, 87 percent were import associated . Since 2008, most imported United States cases have been from the European Region  or the Philippines. Measles in the Philippines in 2014 was linked to 23 outbreaks and 383 cases in the United States in 2014 . In 2014, the United States had 668 cases reported from 27 states, representing the greatest number since elimination in 2000.
The United States has been experiencing a large multistate measles outbreak that started in California in December 2014 and has spread to 19 additional states and Mexico. Between January 1 and May 1, 2015, 169 cases were reported . The measles virus type in this outbreak is identical to the virus type that caused a large measles outbreak in the Philippines in 2014; this virus type was also identified in 14 other countries . Most cases are occurring in under- and unvaccinated individuals [59-61].
Canada — Outbreaks in Canada occurred in 2007 and 2011 due to importation [44,62]. In 2007, an outbreak including 94 measles cases occurred in Quebec, resulting in transmission within several unrelated networks of unvaccinated individuals despite an estimated overall population immunity of 95 percent . Subsequently, in 2011, Quebec sustained the largest outbreak since elimination, with 21 measles importations linked to a large outbreak in France and 725 cases . A super-spreading event triggered by one importation resulted in sustained transmission and 678 cases. The overall incidence was 9 per 100,000; the highest incidence occurred among adolescents (75 per 100,000), among whom 22 percent had received two vaccine doses. Two-dose recipients had a milder illness and lower risk of hospitalization than single-dose recipients or unvaccinated individuals.
European Region — The WHO-designated European Region established a goal of measles elimination by the year 2015 (revised from 2010 because of ongoing measles outbreaks) . Beginning in late 2009, there has been a sharp increase in measles cases in the Region, primarily in Western Europe in 2011, peaking in 2013 with over 32,000 cases, followed by a 50 percent decline in 2014 . Of the approximately 26,000 cases reported for 2011, an estimated 54 percent occurred in France , and the largest outbreaks in 2014 were in the Russian Federation and Georgia, and continued transmission was also noted in Germany and Krygyzstan . The increase in cases has been primarily attributed to lack of vaccination of susceptible populations. Reasons for lack of vaccination include religious or philosophical beliefs, lack of healthcare access, and anti-vaccination movements [27,55,63,65-67].
African Region — The WHO-designated African Region has established several goals toward measles elimination, yet this region still accounted for 51 percent of all measles-associated death in 2013 . The region set a goal to reduce measles deaths by 98 percent in 2012 compared with year 2000 estimates ; in addition, in 2011 a goal of measles eradication by 2020 was set . The launch of these initiatives and previous efforts have improved measles immunization coverage rates in children from 53 to 74 percent with the first dose of measles vaccine for nine-month-olds between 2000 and 2013, with 21 percent increase in the number of member states with coverage ≥90 percent . However, efforts to provide a routine second dose have lagged behind, with only 7 percent of member states providing this opportunity. Additionally, "catch-up" vaccinations targeting a wide age range were offered in 43 of the 46 African Region nations by the end of 2008. The improved vaccination rates were associated with a 67 percent reduction in measles cases, from 520,102 cases in 2000 to 171,905 cases in 2013, and an 84 percent decline in mortality . Measles outbreaks continue to occur, and failure to vaccinate has been identified as the primary cause.
Western Pacific Region — The WHO-designated Western Pacific Region established a target year of 2012 for measles elimination in 2005; this goal that has not been met . For some nations in the Region, measles elimination is hampered by inadequate surveillance and inadequate public health services. Between 2000 and 2013, there was an 82 and 88 percent decline in cases and mortality rates, respectively . A surge in cases was noted in 2008, but dramatic declines were noted after this and, as of mid-2009, 24 of the 37 countries and areas that comprise the Region were thought to have eliminated or nearly eliminated measles. The Republic of Korea declared measles eliminated in 2006. The majority of measles cases occurred in China in 2008 . An outbreak occurred in Japan from 2007 to 2008, which led to secondary imported cases in Canada and the United States . In addition, an epidemic in the Philippines in 2014 increased cases in the region along with outbreaks in Vietnam and continued increases in the number of cases in China. Despite this, the region has a two-dose measles vaccine coverage rate of just above 90 percent. The Region had over 78,000 measles cases in 2014 [39,71].
Eastern Mediterranean Region — The WHO-designated Eastern Mediterranean Region set a goal of measles elimination by 2010 in 1997; this has not been achieved. Implementing measles control has been a challenge in some areas, in part due to civil unrest, natural disasters, and inadequate public health systems [38,72]. Overall measles cases have declined; in the early 1980s, there were approximately 200,000 cases identified annually , but, in 2013, 20,885 cases were identified . Measles-related deaths are estimated to have fallen by 49 percent from 2000 to 2013, with resurgence in cases noted starting in 2008 mainly because of large outbreaks in several countries with conflicts and insecurity . In 2012, of the 23 member countries, administration of the primary dose of measles immunization was recommended at 9 months of age in 12 countries (52 percent) and at 12 to 15 months in 11 countries (48 percent). Twenty countries (87 percent) had measles vaccination schedules with at least two doses and overall coverage hovering around 83 percent.
Southeast Asia Region — The WHO-designated Southeast Asia Region improved measles vaccine coverage between 2000 to 2013 by 24 percent; 78 percent of member states offered two doses of vaccine which was associated with a 63 percent reduction in measles deaths . This Region had approximately 31,000 measles deaths in 2013, representing the second highest mortality rate globally (26 percent). This Region includes India, identified as the only WHO-designated "priority country" that has not implemented the WHO measles control strategies [16,38,74].
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)")
●Measles is a highly contagious viral illness characterized by fever, malaise, rash, cough, coryza, and conjunctivitis that occurs worldwide; it remains endemic in areas with low vaccination rates, particularly in the developing world. It has been targeted for eradication given the favorable biologic characteristic that humans are the only reservoir. However, due to social and political factors and high transmissibility, elimination has been achieved in very few areas of the world. (See 'Introduction' above.)
●In the prevaccine era, ≥90 percent of children acquired measles by age 15. Following implementation of routine childhood vaccination at age 12 to 15 months, the age of peak measles incidence during epidemics in the United States shifted to less than 12 months. This is the time at which transplacentally acquired maternal antibodies are no longer protective in the child if the mother has vaccine-induced immunity. (See 'Epidemiology' above.)
●Measles is highly contagious; the attack rate in a susceptible individual exposed to measles is 90 percent. The period of contagiousness is estimated to be from five days before the appearance of rash to four days afterward. Infectious droplets from the respiratory secretions of a patient with measles can remain airborne for up to two hours. Therefore, the illness may be transmitted in public spaces, even in the absence of person-to-person contact. (See 'Transmission' above.)
●Individuals at risk for measles include children too young to be vaccinated, those who have not been vaccinated for medical or other reasons, those who have not received a second dose of measles vaccine, and those for whom the vaccine failed to elicit a protective immune response (a very small fraction of those immunized). Travel to areas where measles is endemic or contact with ill persons arriving from these countries increases the risk of exposure to measles. (See 'Individuals at risk' above.)
●The live attenuated measles vaccine was introduced in the United States in 1967; since that time, the number of cases has fallen by approximately 99 percent. Measles is no longer considered an endemic disease in the United States, although isolated outbreaks due to measles importation continue to occur. (See 'United States' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge Jorge Barinaga, MD, MS, and Paul Skolnik, MD, FACP, FIDSA, who contributed to an earlier version of this topic review.
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