In this time of modern medicine and vaccines, Americans have forgotten the devastation, morbidity, and latent conditions caused by measles. Unsubstantiated claims that suggest an association between the measles vaccine and autism have resulted in reduced vaccine use and contributed to a recent resurgence of measles in countries where immunization rates have fallen to below the level needed to maintain herd immunity. This course will prepare healthcare professional to participate in prevention and to identify and respond to measles outbreak.
I was a 3 1/2 year old female toddler obsessed with her first goal…becoming a “Big Sister”. I wasn’t particular about the sex of the individual I was going to become a “Big Sister” to, I just wanted one. I begged and pleaded with my parents to no avail. My suggestion was usually met with smiles or being reminded that I was already a “Little Sister”. This statement failed to provide me with any consolation.
While I was playing in the front room, the kitchen phone rang. My mother’s voice changed during the conversation. Her comment, “Come now!” caught my attention. She called to my father, whispered something to him that prompted him to run down the basement stairs and return carrying my old crib. My mother, meantime, had run into the front bedroom where my sister and I slept and began moving our twin beds around to make more room for the crib. She changed the sheets on both our twin beds. She, also, then ran into the master bedroom and began hurriedly changing the sheets on my parents bed. Boy, this seemed like a lot of work for a little baby! Finally, I thought, my new baby sister or brother was arriving. I ran back to the screen door in the living room scanning the sky for the evidence of the stork.
Instead of the stork, my uncle drove up. He ran carrying my new baby brother or sister in his arms and placed him/her in the crib. My parents, meanwhile, had run past me and were carrying my two cousins from the car into the front bedroom. My uncle, having already run by me back to the car, was now carrying my oldest cousin in his arms and placed her in my parents’ bed.
Where was the stork? Why are my cousins here? When are they leaving? Why was my new brother or sister ugly i.e. red, crying eyes, whimpering, with red and white dots? My cousins didn’t seem to want to play…so what’s all the fuss? And why was my aunt just leaning against the passenger side door with her eyes closed? Why did my uncle just drive off so fast and my mother was crying when she looked at her sister?
The days faded into weeks and then into what seemed like years. The “baby” and my cousins seemed never to be going home. My parents were always bathing them gently in the bathtub, coaxing them to eat or drink anything, rocking them in the rocker, applying soothing ointment to their skin etc. The only redeeming asset to this disturbance in my life seemed to be the overabundance of popsicles I could abscond. To my great dismay, the “baby” turned out to be my newest cousin. Once again I resorted to pleading and begging.
Forty years later, all things were clarified concerning this episode in my life. My aunt and all four cousins had the measles. My aunt was hospitalized for three weeks and almost died. While she was hospitalized, my uncle came down with the measles. Due to the care given to my four cousins by my parents, they all survived to plague me throughout my lifetime. My father, mother, sister and I had already had the measles so were immune. And, by the way, I never became a “Big Sister”.
After completing this course, the learner will be able to meet the following objectives:
Describe the epidemiology of measles in the United States and worldwide.
List the modes of transmission of the measles virus.
Relate the evidence which constitutes immunity to the measles virus.
Describe the signs and symptoms of the prodromal, enanthem and exanthem phases of the measles infection.
Relate the goals and interventions used in the management and treatment of the measles infected individual.
Compare and contrast medications used in the prevention or treatment of measles including recommendations and contraindications/precautions.
Relate the prognosis of survival of measles.
Measles, also known as morbilli, rubeola, or red measles, is a highly contagious infection caused by the measles virus. The measles virus is a single-stranded, negative-sense, enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae.
Molecular epidemiology of measles viruses is an important component in outbreak investigations and for global surveillance of circulating wild-type measles strains i.e. measles viruses that are endemic to certain populations around the globe. During outbreaks, measles vaccine is administered to help control the outbreak, and in these situations, vaccine reactions may be mistakenly classified as measles cases. A small proportion of measles vaccine recipients experience rash and fever 10 – 14 days following vaccination. The vaccine strain of measles virus can be distinguished from wild-type measles viruses by determination of the genotype from clinical samples or virus isolates.
Wild-type measles viruses have been divided into distinct genetic groups, referred to as genotypes, based on the nucleotide sequences of their hemagglutinin (H) and nucleoprotein (N) genes, which are the most variable genes on the viral genome.
The 450 nucleotides encoding the carboxy-terminal 150 amino acids of the nucleoprotein has up to 12% nucleotide variation between genotypes. The 450 nucleotides that encode the carboxy-terminal region of the nucleoprotein (N-450) are required for determination of the genotype. The measles genotyping protocol is available from the Centers for Disease Control and Prevention (CDC).
For each genotype, a reference strain is designated for use in genetic analysis (phylogenetic analysis), usually the earliest known virus isolation of that group. The means of referring to the genotypes has been standardized using alphabetical designations for the main groupings (clades). Within the main clades, numerals are added to identify the individual genotypes.
The following 19 genotypes have been detected since 1990:
A*, B2, B3, C1, C2, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11, G2, G3, H1, H2
*Vaccine strains Moraten, Edmonston, Zagreb are all genotype A.
There were 2 putative wild-type cases of measles identified as genotype A in 2008.
During 2011, 8 genotypes were identified by global surveillance:
B2, B3, D4, D8, D9, D11, G3, H1
Initial infection and viral replication occur locally in tracheal and bronchial epithelial cells. After 2 - 4 days, the measles virus infects local lymphatic tissues, perhaps carried by pulmonary macrophages. Following the amplification of the measles virus in regional lymph nodes, a predominantly cell-associated viremia disseminates the virus to various organs prior to the appearance of the rash.
Measles virus infection causes a generalized immunosuppression marked by decreases in delayed-type hypersensitivity, interleukin (IL)-12 production, and antigen-specific lymphoproliferative responses that persist for weeks to months after the acute infection. Immunosuppression may predispose individuals to secondary opportunistic infections, particularly bronchopneumonia; a major cause of measles-related mortality among younger children.
In individuals with deficiencies in cellular immunity, the measles virus causes a progressive and often fatal giant cell pneumonia.
In immunocompetent individuals, wild-type measles virus infection induces an effective immune response, which clears the virus and results in lifelong immunity.
The first scientific description of measles and its distinction from smallpox and chickenpox is credited to the Persian physician Rhazes (860 - 932), who published The Book of Smallpox and Measles in the 9th century. Given what is now known about the evolution of measles, this account is remarkably timely, as recent work that examined the mutation rate of the virus indicates that the measles virus emerged from rinderpest (Cattle Plague) as a zoonotic disease between 1100 and 1200 AD, a period that may have been preceded by limited outbreaks involving a virus not yet fully acclimated to humans. This agrees with the observation that measles requires a susceptible population of greater than 500,000 to sustain an epidemic, a situation that occurred in historic times following the growth of medieval European cities.
Measles is an endemic disease, meaning it has been continually present in a community, and thus many individuals developed resistance. In populations not exposed to measles, exposure to the new disease was devastating.
In 1529, a measles outbreak in Cuba killed two-thirds of the natives who had previously survived smallpox.
In 1531, measles was responsible for the deaths of half the population of Honduras, and had ravaged Mexico, Central America, and the Inca civilization.
In the 1850’s measles killed 20 percent of Hawaii's population.
In 1875, measles killed over 40,000 Fijians, approximately one-third of the population.
In the 19th century, the disease killed 50% of the Andamanese population.
Between roughly 1855 and 2005, measles has been estimated to have resulted in the deaths of about 200 million people worldwide.
Seven to eight million children are thought to have died from measles each year before the vaccine was introduced.
In 1757, Francis Home, a Scottish physician, demonstrated that measles is caused by an infectious agent in the blood of patients.
In 1912, measles became a nationally notifiable disease in the United States, requiring United States healthcare providers and laboratories to report all diagnosed cases. In the first decade of reporting, an average of 6,000 measles-related deaths were reported each year.
The virus was first isolated in 1954 by Nobel Laureate John F. Enders and Dr. Thomas C. Peebles who collected blood samples from several ill students during a measles outbreak in Boston, Massachusetts. They wanted to isolate the measles virus in the student’s blood and create a measles vaccine. The measles virus was isolated from 13-year-old David Edmonton’s blood and adapted and propagated on a chick embryo tissue culture.
In the decade before 1963 when a vaccine became available, nearly all children got measles by the time they were 15 years old. It is estimated 3 to 4 million individuals in the United States were infected with measles every year. Of these, an estimated 400 to 500 died, 48,000 were hospitalized, and 4,000 suffered encephalitis as a complication of measles.
In 1963, John F. Enders and colleagues transformed their Edmonston-B strain of the measles virus into a vaccine and licensed it in the United States.
In 1968, an improved and even weaker measles vaccine, was developed by Maurice Hilleman and colleagues, and began to be distributed. This vaccine, called the Edmonston-Enders (formerly “Moraten”) strain has been the only measles vaccine used in the United States since 1968. The measles vaccine is usually combined with mumps and rubella (MMR), or combined with mumps, rubella and varicella (MMRV).
Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.
In 1978, the CDC set a goal to eliminate measles from the United States by 1982. Although this goal was not met, widespread use of the measles vaccine drastically reduced the rate of measles infections. By 1981, the number of reported measles cases was 80% lower than in the previous year.
However, a 1989 to 1991 measles outbreak among vaccinated school-aged children prompted the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) to recommend a second dose of the MMR vaccine be given to all children. Following widespread implementation of this recommendation and improvements in first-dose MMR vaccine coverage, the reported cases of measles declined even more.
In the years after 1991, the United States witnessed the return of subacute sclerosing panencephalitis among United States children. This is a rare fatal neurologic complication of measles that had all but disappeared after the measles vaccine was introduced in the 1960s.
In 2000, measles was declared eliminated from the United States. Elimination is defined as the absence of endemic measles virus transmission in a defined geographic area, such as a region or country, for 12 months or longer in the presence of a well-performing surveillance system. This was possible due to a highly effective vaccination program and better measles control in the Americas region.
The continued circulation of measles in a community depends on the generation of susceptible hosts by the birth of children. In communities which generate insufficient new hosts the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number of people capable of supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is about 250,000. To achieve herd immunity, more than 95% of the community must be vaccinated due to the ease with which measles is transmitted from individual to individual.
Measles is one of the first diseases to reappear when vaccination coverage rates decline. Ongoing measles outbreaks are occurring in European countries where rates of vaccination coverage are lower than those in the United States including Austria, Italy, and Switzerland. In June 2008, the United Kingdom's Health Protection Agency declared that, because of a drop in vaccination coverage levels (to 80% - 85% among children age 2 years), measles was again endemic in the United Kingdom, 14 years after it had been eliminated. Since April 2008, two measles-related deaths have been reported in Europe, both in children ineligible to receive the MMR vaccine because of congenital immunologic compromise. Such children depend on herd immunity for protection from the disease, as do children less than 12 months of age, who normally are too young to receive the measles vaccine. Otherwise healthy children with measles are also at risk for severe complications, including encephalitis and pneumonia, which can lead to permanent disability or death.
Sustaining elimination requires maintaining high MMR vaccine coverage rates, particularly among preschool (greater than 90% 1-dose coverage) and school-aged children (greater than 95% 2-dose coverage). High coverage levels provide herd immunity, decreasing everyone’s risk for measles exposure and affording protection to individuals who cannot be vaccinated. However, herd immunity does not provide 100% protection, especially in communities with large numbers of unvaccinated individuals. For the foreseeable future, measles importations into the United States will continue to occur because measles is still common in Europe and other regions of the world. Within the United States, the current national MMR vaccine coverage rate is adequate to prevent the sustained spread of measles. However, importations of measles likely will continue to cause outbreaks in communities that have sizeable clusters of unvaccinated individuals.
A measles case is considered confirmed if it is laboratory-confirmed or meets the clinical case definition i.e. an illness characterized by a generalized rash lasting 3 or more days, a temperature of ≥ 101°F [≥38.3°C], and cough, coryza, and/or conjunctivitis and is linked epidemiologically to a confirmed case. Confirmed measles cases in the United States are reported by state and local health departments to the CDC using standard case definitions and case classifications.
An outbreak of measles is defined as a chain of transmission with three or more confirmed cases.
Measles cases are reported by state health departments to the CDC, and confirmed cases are reported via the National Notifiable Disease Surveillance System (NNDSS) using standard case definitions.
When the measles vaccine was first licensed in 1963, the practice of administering two doses of live-attenuated measles vaccine to children was implemented to prevent school outbreaks. The immunization program resulted in a decrease of more than 99% in the reported incidence of measles.
From 1989 to 1991, a major resurgence of measles occurred which affected primarily unvaccinated preschoolers. This measles resurgence resulted in 55,000 cases and 130 deaths. This prompted the recommendation that a second dose of measles vaccine be given to preschoolers. This mass vaccination campaign led to the effective elimination of the endemic transmission of the measles virus in the United States. Subsequently, most reported cases of measles in the United States have been linked to international travel.
By 1997-1999, the incidence of measles had been reduced to a historic low (less than 0.5 cases per million individuals). From 1997 to 2004, the reported incidence was as low as 37-116 cases per year. From November 2002 on, measles was not considered an endemic disease in the United States.
In 2000, the transmission of endemic measles was declared eliminated in the United States.
2004: 34 cases of measles were reported to the CDC. After that all-time low, however, the annual incidence began to increase, with most cases linked either directly or indirectly to international travel. Incomplete vaccination rates facilitated the spread of measles once the virus was imported to the United States.
2005: 66 cases of measles were reported to the CDC. Of these, 34 were linked to a single outbreak in Indiana associated with the return of an unvaccinated 17-year-old American traveling in Romania. Of the 66 cases of measles reported in the United States in 2005, 7 (10.6%) involved infants, 4 (6.1%) involved children age 1 - 4 years, 33 (50%) involved individuals age 5 - 19 years, 7 (10.6%) involved adults age 20 - 34 years, and 15 (22.7%) involved adults older than 35 years.
2006:49 confirmed cases of measles were reported to the CDC.
Summary 2000 through 2007: An average of 63 cases of measles were reported annually to the CDC.
From January to July 31, 2008: 131 cases of measles were reported to the CDC from 15 states and the District of Columbia (DC): Illinois (32 cases), New York (27 cases), Washington (19 cases), Arizona (14 cases), California (14 cases), Wisconsin (7 cases), Hawaii (5 cases), Michigan (4 cases), Arkansas (2 cases), and DC, Georgia, Louisiana, Missouri, New Mexico, Pennsylvania, and Virginia (1 case each). Among the 131 cases of measles, 123 were United States residents, of whom 99 (80%) were less than 20 years of age. Five (4%) of the 123 individuals had received 1 dose of the MMR vaccine, six (5%) had received 2 doses of the MMR vaccine, and 112 (91%) were unvaccinated or had unknown vaccination status. Among these 112 individuals, 95 (85%) were eligible for vaccination, and 63 (66%) of those were unvaccinated because of philosophical or religious beliefs.
Summary January to July 31, 2008: The number of measles cases reported during January 1 - July 31, 2008, remains the highest year-to-date since 1996. This increase was the result of greater viral transmission after importation into the United States, leading to a greater number of importation-associated cases. These importation-associated cases occurred largely among school-aged children who were eligible for vaccination but whose parents chose not to have them vaccinated. One study suggested an increasing number of vaccine exemptions among children who attend school in states that allow philosophical exemptions. Also, to confound the issue, home-schooled children are not covered by school-entry vaccination requirements in many states. The measles outbreaks in Illinois and Washington demonstrated that measles remains a risk for unvaccinated individuals and those who come in contact with them. Each school year, parents should ensure that their children's vaccinations are current, regardless of whether the children are returning to school, attending daycare, or being schooled at home. Adults without evidence of measles immunity should receive at least 1 dose of MMR vaccine.
Summary 2001 – 2008: a median of 56 (range: 37-140) measles cases were reported to the CDC annually.
2011: 118 cases of measles were reported to the CDC from 23 states and New York City from January 1 to May 20, 2011. Among the 118 cases, 105 (89%) were import-associated, of which 46 (44%) were importations from at least 15 countries, 49 (47%) were import-linked, and 10 (10%) were imported virus cases. The source of 13 cases not import-associated could not be determined. Among the 46 imported cases, most were among individuals who acquired the disease in the WHO European Region or South-East Asia Region, and 34 (74%) occurred in United States residents traveling abroad.
Nine outbreaks accounted for 58 (49%) of the 118 cases. The median outbreak size was four cases (range: 3 - 21). In six outbreaks, the index case acquired measles while abroad. The source of the other three outbreaks could not be determined. Transmission occurred in households, child care centers, shelters, schools, emergency departments, and at a large community event. The largest outbreak occurred among 21 individuals in a Minnesota population in which many children were unvaccinated because of parental concerns about the safety of the MMR vaccine. That outbreak resulted in exposure of many individuals and infection of at least seven infants too young to receive the MMR vaccine.
Individuals ranged in age from 3 months to 68 years: 18 (15%) were less than 12 months of age, 24 (20%) were 1 – 4 years of age, 23 (19%) were 5 – 19 years of age, and 53 (45%) were age 20 or older. Measles was laboratory-confirmed in 105 (89%) cases, and the measles virus RNA was detected in 52 (44%) cases.
Unvaccinated individuals accounted for 105 (89%) of the 118 cases. Among the 45 residents of the United States age 12 months - 19 years who acquired measles, 39 (87%) were unvaccinated, including 24 whose parents claimed a religious or personal exemption and eight who missed opportunities for vaccination. Among the 42 residents of the United States age 20 or older who acquired measles, 35 (83%) were unvaccinated, including six who declined to be vaccinated because of philosophical objections to vaccination. Of the 33 United States residents who were vaccine-eligible and had traveled abroad, 30 were unvaccinated and one had received only 1 of the 2 recommended doses.
Of the 118 cases, 47 (40%) resulted in hospitalization. Nine individuals had pneumonia. None had encephalitis. None died. All but one hospitalized individual were unvaccinated. The vaccinated individual reported having received 1 dose of measles-containing vaccine and was hospitalized for observation only. Hospitalization rates were highest among infants and children less than 5 years of age (52%), but rates also were high among children and adults older than 5 years (33%).
The unusually large number of importations into the United States in the first 19 weeks of 2011 was related to recent increases in measles in countries visited by United States travelers. The most frequent sources of importation in 2011 were countries in the WHO European Region, which has accounted for the majority of measles importations in the United States since 2005 and the South-East Asia Region. During 2011, 33 countries in the WHO European Region have reported an increase in measles. France, the source of most of the importations from the European Region, experienced a large outbreak, with approximately 10,000 cases reported during the first 4 months of 2011, including 12 cases of encephalitis, a complication that often results in permanent neurologic sequelae, 360 cases of severe measles pneumonia, and six measles-related deaths.
Children and adults who remained unvaccinated and developed measles also put others in their community at risk. For infants too young for routine vaccination (age less than 12 months) and individuals with medical conditions that contraindicated measles immunization, the risk for the complications of measles was particularly high. These individuals depend on high MMR vaccination coverage among those around them to protect them from exposure. In the United States in 2011, infants less than 12 months of age accounted for 15% of cases and 15% of hospitalizations. In Europe in recent years, measles has been fatal for several children and adolescents, including some who could not be vaccinated because they were immune compromised.
Rapid control efforts by state and local public health agencies, which are both time intensive and costly, have been a key factor in limiting the size of outbreaks and preventing the spread of measles into communities with increased numbers of unvaccinated individuals. Nonetheless, maintenance of high 2-dose MMR vaccination coverage is the most critical factor for sustaining elimination. For measles, even a small decrease in coverage can increase the risk for large outbreaks and endemic transmission, as occurred in the United Kingdom in the past decade.
An annual total of 220 cases of measles was reported to the CDC in 2011.
Summary 2001 through 2011: According to the CDC, cases continued to be caused by the measles virus being brought into the country by travelers from abroad, with spread occurring largely among unvaccinated individuals. In 88% of the cases reported between 2000 and 2011, the measles virus originated from a country outside the United States and 2 out of every 3 individuals who developed measles were unvaccinated. A review by the CDC in 2014 reported a total of 911 cases of measles from 2001 to 2011, with an annual median number of 61 cases and concluded that "the elimination of endemic measles, rubella, and Congenital Rubella Syndrome (CRS) has been sustained in the United States”.
January 1 – August 24, 2013: A total of 159 cases were reported to the CDC from 16 states and New York City. Among the 159 cases, 157 (99%) were import-associated, and two had an unknown source. Forty-two (26%) importations (23 returning United States residents and 19 visitors to the United States) from 18 countries were reported, and 21 (50%) of the importations were from the WHO European Region. Genotypes identified to date are D8 (47 cases), B3 (six cases), H1 (four cases), D9 (three cases), and D4 (two cases).
During 2013, eight outbreaks accounted for 77% of the cases, and outbreaks ranged from 3 to 58 cases. The largest outbreak occurred in New York City. None of these individuals had documented vaccination status at the time of exposure, including 12 (21%) who were less than 12 months of age. Of those who were eligible for vaccination, 31 (67%) had objected or had parental objection to vaccination because of religious or philosophical beliefs. The second largest outbreak, in North Carolina (23 cases, including a California resident), occurred mainly among individuals not vaccinated because of personal belief exemptions. During an outbreak in Texas, 20 confirmed cases were reported as of August 24, 2013 among members of a church community. Nineteen (95%) cases were in individuals older than 12 months, and 17 (85%) of the individuals were unvaccinated. The index patient was an adult with unknown measles vaccination history who traveled to Indonesia.
Individuals ranged in age from 0 days to 61 years: 18 (11%) were less than 12 months of age, 40 (25%) were 1 - 4 years old, 58 (36%) were 5 - 19 years of age, and 43 (27%) were age 20 or older. Of the 159 cases, 17 (11%) individuals required hospitalization, including four diagnosed with pneumonia. No deaths were reported.
Most of the 159 cases were in individuals who were unvaccinated (131 or 82%) or had unknown vaccination status (15 or 9%). Thirteen (8%) of the individuals had been vaccinated, of whom three had received 2 doses of the MMR vaccine. Among the 140 United States residents who acquired measles, 117 (84%) were unvaccinated, and 11 (8%) had unknown vaccination status. Of those who were unvaccinated, 92 (79%) had philosophical objections to vaccination, six (5%) had missed opportunities for vaccination, 15 (13%) occurred among infants less than 12 months of age who were not eligible for vaccination, and for four (3%) the reason for no vaccination was unknown. Among the 21 United States residents who had traveled abroad and were 6 months or older, 14 (67%) were unvaccinated, five (24%) had unknown vaccination status, and two had received 1 dose of the MMR vaccine.
Summary January 1 to August 24, 2013: The WHO European Region continues to be the source of imported cases, a popular destination for travelers from the United States and an area where measles continues to circulate. Measles importations were reported by United States residents, most of whom were 6 months or older and unvaccinated.
January 1 to May 23, 2014: 288 confirmed cases of measles were reported to the CDC. Of the 288 cases, 280 (97%) were associated with importations from at least 18 countries. The source of measles acquisition could not be identified for 8 (3%) of the cases. Forty-five direct importations (40 residents of the United States returning from abroad and five foreign visitors) were reported. Almost half (22 or 49%) of these importations were travelers returning from the Philippines, where a large outbreak occurred beginning in October 2013. Imported cases were also associated with travel from other countries in the WHO Western Pacific Region (7 cases), as well as, countries in the WHO South-East Asia (8 cases), European (4 cases), Americas (3 cases), and Eastern Mediterranean (1 case) regions. Measles genotype information was obtained from 103 (36%) of the 288 measles cases. Four measles virus genotypes were identified: B3 (67 cases), D9 (23 cases), D8 (12 cases), and H1 (one case).
Measles cases were reported from 18 states and New York City. Most cases were reported from Ohio (138 cases), California (60 cases), and New York City (26 cases). Fifteen outbreaks accounted for 227 (79%) of the 288 cases. The median outbreak size was five measles cases (range: 3 - 38). There was an ongoing outbreak involving 138 individuals, occurring primarily among unvaccinated Amish communities in Ohio.
Individuals with reported measles cases in 2014 ranged in age from 2 weeks to 65 years: 18 (6%) were less than 12 months of age, 48 (17%) were 1 - 4 years old, 71 (25%) were5 - 19 years of age, and 151 (52%) were 20 years of age or older. Forty-three (15%) were hospitalized, and complications included pneumonia (5 cases), hepatitis (1 case), pancytopenia (1 case), and thrombocytopenia (1 case). No cases of encephalitis or deaths were reported.
Most of the 288 measles cases reported in 2014 were in individuals who were unvaccinated (200 or 69%) or who had an unknown vaccination status (58 or 20%). Thirty (10%) were in individuals who were vaccinated. Among the 195 United States residents who had measles and were unvaccinated, 165 (85%) declined vaccination because of religious, philosophical, or personal objections, 11 (6%) were missed opportunities for vaccination, and 10 (5%) were too young to receive vaccination.
Summary January 1 to May 23, 2014: As of May 23, 2014, a total of 40 importations were reported among unvaccinated returning United States travelers. Among these, 22 acquired measles in the Philippines, where 32,030 measles cases (26,014 suspected cases and 6,016 confirmed cases) and 41 measles deaths were reported from January 1 through . The large number of importations from the Philippines highlights how importations are related to increases in measles incidence in countries that are common destinations for United States travelers. Because measles remains endemic in countries in five out of the six WHO regions of the world, including India, where six importations occurred this year, the source of imported cases could be any country where measles continues to circulate. This underscores the importance of ensuring age-appropriate vaccination for all individuals before international travel to any region of the world.
In the three largest outbreaks of 2014, which accounted for over half of all cases, transmission occurred after introduction of measles into communities with pockets of individuals who were unvaccinated because of philosophical or religious beliefs. Although high population immunity throughout the United States (through maintaining equal to or greater than 90% MMR vaccine coverage among children age 19 - 35 months and adolescents) prevented spread from most importations, coverage varied at the local level, and unvaccinated children tend to cluster geographically, increasing the risk for outbreaks. Thus, maintaining high measles vaccination coverage is critical to preventing large measles outbreaks in the United States, and to protect and limit spread to infants too young to be vaccinated and to individuals who cannot be vaccinated because of medical contraindications.
December 2014 to February 2015: On January 5, 2015, the California Department of Public Health (CDPH) was notified about a suspected measles case. The unvaccinated, 11 year old child was hospitalized with rash onset on December 28, 2014. During the exposure period, the only notable travel history was a visit to one of two adjacent Disney theme parks located in Orange County, California. Also on January 5, 2015, the CDPH received reports of four additional suspected measles cases in California residents and two in Utah residents, all of whom reported visiting one or both Disney theme parks during December 17 – 20, 2014. By January 7, 2015 seven California measles cases had been confirmed, and the CDPH issued a press release and an Epidemic Information Exchange (Epi-X) notification to other states regarding this outbreak.
As of February 11, 2015, a total of 125 measles cases with rash which occurred between December 28, 2014 and February 8, 2015, had been confirmed in residents of the United States connected with the California outbreak.
Of these 125 measles cases, 110 individuals were California residents. Thirty-nine (35%) of the Californians had visited one or both of the two Disney theme parks between December 17 – 20, 2014 where they are thought to have been exposed to themeasles virus. Thirty-seven (34%) had an unknown exposure source and 34 (31%) were secondary cases. Of the 34 secondary cases, 26 cases were household or close contacts, and 8 were exposed in a community setting. Five (5%) of the California residents reported being in one or both of the two Disney theme parks during their exposure period of December 17 – 20, 2014 but their source of infection remains unknown. In addition, 15 cases linked to the two Disney theme parks were reported in seven other states: Arizona (7 cases), Colorado (1 case), Nebraska (1 case), Oregon (1 case), Texas (1 case), Utah (3 cases), and Washington (2 cases), as well as, linked cases reported in two neighboring countries, Mexico (1 case) and Canada (10 cases).
Among the 110 California residents, forty-nine (45%) were unvaccinated. Twelve of the unvaccinated were infants too young to be vaccinated. Among the 37 remaining vaccine-eligible residents, 28 (76%) were intentionally unvaccinated because of personal beliefs, and 1 was on an alternative plan for vaccination. Among the 28 intentionally unvaccinated residents, 18 were children less than 18 years of age, and 10 were adults. All California residents ranged in age from 6 weeks to 70 years with the median age being 22 years.Among the 84 California residents with known hospitalization status, 17 (20%) were hospitalized.
The source of the initial Disney theme park exposure has not been identified. Specimens from 30 California residents were genotyped. All were measles genotype B3, which had caused a large outbreak in the Philippines, but had also been detected in at least 14 countries and at least 6 states of the United States in the previous 6 months.
January 4 – April 2, 2015: a total of 159 measles cases (155 residents of the United States and four foreign visitors) from 18 states and the District of Columbia were reported to the CDC. Over 80% of the cases occurred among individuals who were unvaccinated or had unknown vaccination status. Four outbreaks had occurred, with one accounting for 70% of all measles cases as of April 2, 2015.Individuals ranged in age from 6 weeks to 70 years: 26 (16%) were less than 12 months of age, 18 (12%) were 1 – 4 years of age, 27 (17%) were ages 5 – 19 years, 58 (36%) were ages 20 - 39 years, and 30 (19%) were age 40 or older. Twenty-two individuals (14%) were hospitalized, including five with pneumonia. No other complications or deaths were reported.
A total of 111 cases (70%) were associated with the outbreak that originated in late December 2014 in Disney theme parks in Orange County, California. The source of the initial exposure was not identified, but measles cases associated with this outbreak have been reported in 7 states of the United States, Mexico and Canada. Measles was laboratory confirmed in 101 (91%) of these cases, either by detection of measles-specific IgM or of measles virus RNA. The B3 genotype was identified in specimens from at least 40 individuals associated with this outbreak. B3 is a common measles genotype that has been identified in multiple states and countries. Other smaller measles outbreaks in 2015 without a link to Disney theme parks have been reported in Illinois (15 cases), Nevada (9 cases), and Washington (5 cases).
The majority of the 159 patients with reported measles in the 2015 outbreaks were either unvaccinated (71 or 45%), had unknown vaccination status (60 or 38%), or had received the measles vaccine (28 or 18%). Among the 68 residents of the United States who had measles and were unvaccinated, 29 (43%) cited philosophical or religious objections to vaccination, 27 (40%) were ineligible because they were too young to receive vaccination or had a medical contraindication (1 case), 3 (4%) represented missed opportunities for vaccination, and 9 (13%) had other reasons for not being vaccinated.
Of the 159 measles cases, 153 (96%) were import-associated. Ten cases were classified as direct importations, (6 among unvaccinatedresidents of the United States returning from overseas travel, of whom 3 were 6 – 11 months old (age-eligible for vaccination before departure), and 4 among foreign visitors. Countries associated with direct importations included Azerbaijan, China, Germany, India, Indonesia, Kyrgyzstan, Pakistan, Qatar, Singapore, and United Arab Emirates (one import each).
January 4 – April 2, 2015:As in previous years, a sizeable proportion of United States residents who became infected with measles had an unknown vaccination status. This occurred primarily among adults and reflects the lack of immunization data in registries on adults in the United States. Among the United States residents who were confirmed as, the numbers who were ineligible for vaccination or who cited philosophical or religious beliefs as the reason they declined vaccination were similar. Exemptions from mandated immunizations have been shown to increase the risk for acquiring measles, as well as, increasing the risk of a measles outbreak at the community level. Exemption rates are higher in jurisdictions where exemption requirements are procedurally easier to be met.
International travel to countries where measles is endemic is a well-known risk factor for measles, and measles importations continue to occur in the United States. United States residents can also be exposed to measles in the United States itself at venues with large numbers of international visitors, such as tourist attractions and airports. This outbreak illustrates the continued importance of ensuring high measles vaccination coverage in the United States.
Because of ongoing importations of measles to the United States, healthcare providers should suspect measles in individuals with a febrile rash illness and clinically compatible symptoms (e.g., cough, coryza, and/or conjunctivitis) who have recently traveled abroad or have had contact with travelers.
Because individuals with measles often seek medical care, early recognition of suspected measles cases and implementation of appropriate infection control measures are vital to reduce transmission in healthcare settings. Where possible, because of the high transmissibility of measles, individuals with suspected measles should be promptly screened before entering waiting rooms and appropriately isolated (i.e., in an airborne isolation room or, if not available, in a separate room with the door closed), or have their office appointments scheduled at the end of the day to prevent exposure of other individuals.
To assist state and local public health departments with rapid investigation and control efforts to limit the spread of disease, suspected measles cases should be reported to local health departments immediately and specimens obtained for measles testing, including viral specimens for confirmation and genotyping. State health departments should notify the CDC about cases of measles within 24 hours of detection.
In the United States, recommendations for the MMR vaccination include a single dose at age 12 - 15 months and a second dose at the time of school entry (ages 4 – 6). Vaccination as early as 6 months of age is recommended for United States children traveling abroad and is sometimes recommended within communities in the United States during outbreaks of the measles.
All individuals who intend to travel internationally should be up-to-date on their measles vaccination and other vaccinations recommended for countries they might visit. These recommendations include:
a single dose of the MMR vaccine for infant travelers aged 6 - 11 months prior to international travel and
2 doses of the MMR vaccine, administered at least 28 days apart, for children age 12 months or older or have other evidence of immunity to measles
For adults with no evidence of immunity to measles, 1 dose of the MMR vaccine is recommended unless the adult is in a high-risk group (i.e., healthcare personnel, international travelers, or students at post-high school educational institutions), in which case, 2 doses of the MMR vaccine are recommended unless they have other evidence of immunity.
Measles is endemic in many countries, and exposures might occur in airports and in countries of travel.
Despite maintenance of measles elimination in the United States, importations from endemic countries continue to occur and have caused an unusually high number of measles cases in 2014. The most frequent sources of importations were unvaccinated United States travelers returning from abroad, with subsequent transmission among clusters of unvaccinated individuals. Encouraging timely delivery of measles vaccination for individuals traveling internationally and sustaining high vaccination coverage in the United States in accordance with the Advisory Committee on Immunization Practices (ACIP) routine immunization schedule are essential to limit measles importations and the spread of the disease. To help expedite public health containment strategies, healthcare providers should maintain a high awareness of measles, implement appropriate infection control measures when measles is suspected, and promptly report suspected cases to their local health departments.
Healthcare providers should remind individuals who plan to travel internationally, including travel to large international events and gatherings (e.g., the 2014 FIFA World Cup in Brazil), of the increased and encourage timely vaccination of all individuals six months or older who lack evidence of immunity to measles. Healthcare providers should encourage vaccination of all eligible individuals who do not have other evidence of measles immunity.
Maintenance of high 2-dose MMR vaccine coverage has been crucial in limiting the spread of measles from importations in the United States. Most measles importations occur when citizens of the United States travel abroad and have not been appropriately vaccinated. Therefore, it is important to encourage timely delivery of measles vaccination to United States residents before overseas travel. In addition, early detection of cases and rapid public health response to outbreaks can serve to limit the spread of illness.
Importations of measles into communities with unvaccinated individuals can lead to measles cases and outbreaks in the United States. Maintenance of high vaccination coverage, ensuring timely vaccination before travel, and early detection and isolation of cases are key factors to limit importations and the spread of the disease.
In developing countries, measles affects 30 million children a year and causes 1 million deaths. Measles causes 15,000 - 60,000 cases of blindness per year.
In 1998, the cases of measles per 100,000 total population reported to the World Health Organization (WHO) was 1.6 in the Americas, 8.2 in Europe, 11.1 in the Eastern Mediterranean region, 4.2 in South East Asia, 5.0 in the Western Pacific region, and 61.7 in Africa. Only 187 confirmed cases were reported in the Western Hemisphere (mainly in Venezuela, Mexico, and the United States) in 2006.
Between 2000 and 2008, the number of worldwide measles cases reported to the WHO and the United Nations Children’s Fund (UNICEF) declined by 67% (from 852,937 to 278,358). During this same 8-year period, global measles mortality dropped by 78%. However, it is believed that global measles incidence and mortality remain underreported, with many countries, particularly those with the highest disease burden, lacking complete, reliable surveillance data.
Since 2008, France has been experiencing an outbreak of measles, which has not yet begun to slacken. Over the same period, outbreaks have also been occurring in the 46 countries of the WHO African Region. Worldwide, most reported cases of measles continue to be from Africa.
In 2011, the WHO estimated that there were about 158,000 deaths caused by measles. This was down significantly from 630,000 deaths in 1990.
As of 2013, measles remains the leading cause of vaccine-preventable deaths in the world. In developed countries, death occurs in 1 to 2 cases out of every 1,000 (0.1% - 0.2%). In populations with high levels of malnutrition and a lack of adequate healthcare, mortality can be as high as 10%. In cases with complications, the rate may rise to 20% -30%. In 2012, the number of deaths due to measles was 78% lower than in 2000 due to increased rates of immunization among United Nation (UN) member states.
Even in countries where vaccination has been introduced, rates may remain high. Measles is a leading cause of vaccine-preventable childhood mortality. Worldwide, the fatality rate has been significantly reduced by a vaccination campaign led by partners in the Measles Initiative: the American Red Cross, the United States' Centers for Disease Control and Prevention (CDC), the United Nations Foundation, UNICEF and the WHO. Globally, measles fell 60% from an estimated 873,000 deaths in 1999 to 345,000 in 2005. Estimates for 2008 indicate deaths fell further to 164,000 globally, with 77% of the remaining measles deaths in 2008 occurring within the Southeast Asian region.
In 2013 - 2014 there were almost 10,000 cases in 30 European countries. Most cases occurred in unvaccinated individuals and over 90% of cases occurred in the following five European nations: Germany, Italy, the Netherlands, Romania, and the United Kingdom.
Five out of six WHO regions have set goals to eliminate measles, and at the 63rd World Health Assembly in May 2010, delegates agreed a global target of a 95% reduction in measles mortality by 2015 from the level seen in 2000, as well as, to move towards eventual eradication. However, no specific global target date for eradication has yet been agreed to as of May 2010.
Region of the Americas
Eastern Mediterranean Region
South-East Asia Region
Western Pacific Region
Measles, historically, has been thought to be a disease of childhood. Measles infection, though, can occur in unvaccinated or partially vaccinated individuals of any age or in those with compromised immunity.
Unvaccinated young children are at the highest risk. Age-specific attack rates may be highest in susceptible infants younger than 12 months, school-aged children, or young adults, depending on local immunization practices and incidence of the disease. Complications such as otitis media, bronchopneumonia, laryngotracheobronchitis (i.e. croup), and diarrhea are more common in young children.
In heavily populated, underdeveloped countries, measles is most common in children younger than 2 years.
Unvaccinated males and females are equally susceptible to infection by the measles virus. Following acute measles, increased mortality has been observed among females of all ages, but it is most marked in adolescents and young adults. Excessive non – measles related mortality has also been observed among female recipients of high-titer measles vaccines in Senegal, Guinea Bissau, and Haiti. Measles affects people of all races.
In temperate areas, the peak incidence of measles infection occurs during late winter and spring.
The measles virus is a highly contagious airborne virus which lives in the nose and throat mucus of an infected individual. Measles spreads when an infected individual breathes, coughs or sneezes. The measles virus can also live for up to two hours in an airspace where the infected individual breathed, coughed or sneezed. If other individuals breathe the contaminated air or touch an infected surface, then touch their eyes, nose, or mouth, they can become infected. Thus, the virus can be transmitted by direct contact with infectious droplets on surfaces and in the air for up to two hours after an infected individual leaves an area.
Nine out of ten individuals (90%) who share living space with an infected individual and are not immune will catch the measles. Infected individuals are infectious to others from four days before to four days after the start of the rash. Individuals usually only get measles once.
Measles is a disease of humans. The measles virus is not spread by any other animal species.
The American Academy of Pediatrics released updated measles guidelines in response to the national outbreak of the disease. The new guidelines feature changes in the evidence required for measles immunity, the use of immune globulin, vaccination for healthcare personnel, and the management of individuals at high risk for catching measles.
Any of the following constitutes evidence of immunity to measles:
Risk factors for measles viral infection in all age groups include the following:
Healthcare providers should consider measles when evaluating individuals with a febrile rash. Ascertain the individuals:
The incubation period from exposure to onset of measles symptoms ranges from 7 to 14 days (average, 10 - 12 days). Individuals are contagious from 1 - 2 days before the onset of symptoms.Healthy children are considered to be contagious from 4 days before to 4 days after the rash appears. Immunocompromised individuals can be contagious during the duration of the illness.
Prodromal Phase (Early or Premonitory Symptoms of the Disease)
Measles typically begins with:
Catarrhal inflammation of the respiratory tract occurs concomitantly with the ocular symptoms or soon thereafter resulting in the coughing, sneezing and coryza.
Other symptoms may include:
Enanthem (Mucous Membrane Eruption)
The characteristic enanthem generally appears 2 - 4 days after the onset of the prodromal phase and lasts 3 - 5 days. Koplik spots (see images below) - bluish-gray specks or “grains of sand” on a red base – usually develop on the buccal mucosa opposite the second molars.
Koplik spots generally appear 1 - 2 days before the appearance of the rash and last 3 - 5 days after the rash appears.This enanthem begins to slough as the rash appears. Although Koplik spots are diagnostic for measles they are temporary and therefore rarely seen. Their absence does not exclude the diagnosis of measles.Recognizing these spots before an individual reaches their maximum infectiousness can help healthcare providers reduce the spread of the disease.
On average, the rash develops about 14 days after exposure. The characteristic measles rash is classically described as a generalized red maculopapular rash that begins several days after the fever starts. The measles rash appears 3 – 5 days after the symptoms begin and may last up to eight days. The rash is said to "stain", changing color from red to dark brown, before disappearing. Overall, the disease from infection with the measles virus usually resolves after about three weeks. The exanthem (rash) (see images below) usually appears 1 - 2 days after the appearance of Koplik spots. Blanching, erythematous macules and papules usually start behind the ears or on the face or neck at the hairline. Mild pruritus may also occur.
Within 48 hours, the lesions coalesce into patches and plaques that spread cephalocaudally to the trunk and extremities, including the palms and soles, while beginning to regress cephalocaudally, starting from the head and neck. Lesion density is greatest above the shoulders, where macular lesions may coalesce.
The eruption may also be petechial or ecchymotic in nature. Individuals appear most ill during the first or second day of the rash.
Individuals are considered to be contagious from 4 days before to 4 days after the rash appears. The exanthem lasts 5 - 7 days before fading into coppery-brown hyperpigmented patches, which then desquamate.
Immunocompromised individuals may not develop a rash. The rash may be absent in individuals with underlying deficiencies in cellular immunity.
The entire course of uncomplicated measles, from late prodrome to resolution of fever and rash, is 7 - 10 days. Cough may be the final symptom to disappear.
Modified measles is a milder form of measles that occurs in individuals who have received serum immunoglobulin after their exposure to the measles virus. Similar but milder signs and symptoms may still occur. The incubation period may be as long as 21 days.
Atypical measles occurs in individuals who were vaccinated with the original killed-virus measles vaccine between 1963 and 1967. These individuals failed to elicit long-lived protective antibody and a cytotoxic T-lymphocyte response to the measles virus. These individuals have developed incomplete immunity to the measles virus.
After exposure to the measles virus, a mild (sometimes severe) or subclinical prodrome of prolonged high fever, headache, cough, absence of Koplik spots, abdominal pain, myalgias and pneumonia precedes a rash that begins on the hands and feet and spreads centripetally. The atypical rash is accentuated in the skin folds and may be macular, vesicular, petechial, or urticarial. The live-attenuated vaccine replaced the killed-virus measles vaccine in 1967 and is not associated with atypical measles.
Laboratory tests reveal a very low measles antibody titer early in the course of the disease, followed soon thereafter by the appearance of an extremely high measles immunoglobulin G (IgG) antibody titer (e.g. 1:1,000,000) in the serum.
Complications of measles are more likely to occur in individuals younger than 5 years of age or older than 20 years. Individuals at high risk for severe illness and complications from measles include individuals with:
Complications are usually more severe in adults who catch the virus. The death rate in the 1920s was around 30% for measles pneumonia. For every 1,000 children who get measles, one or two will die from it.
Between 1987 and 2000, the case fatality rate across the United States was three measles-attributable deaths per 1000 cases, or 0.3%. In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as high as 28%. In immunocompromised individuals (e.g., people with AIDS etc.) the fatality rate is approximately 30%.
Most complications of measles occur because the measles virus suppresses the hosts’ immune responses, resulting in a reactivation of latent infections or superinfection by a bacterial pathogen. Consequently, pneumonia, whether due to the measles virus itself, to tuberculosis, or to another bacterial etiology, is the most frequent complication.
All individuals with complications, no matter what age, may need to be hospitalized and could face death.
Common measles complications may include:
Severe complications may include:
Subacute sclerosing panencephalitis (SSPE), a very rare, fatal complication of measles, is a degenerative CNS disease that can result from a persistent measles infection which was acquired earlier in life. SSPE generally develops 7 to 10 years (the mean incubation period for SSPE is approximately 10.8 years) after an individual has measles, even though the individual seems to have fully recovered from the illness. Among individuals who contracted measles during the resurgence in the United States in 1989 to 1991, 4 to 11 out of every 100,000 were estimated to be at risk for developing SSPE. The risk of developing SSPE may be higher for an individual who gets measles before they are two years of age. Since measles was eliminated in 2000, SSPE is rarely reported in the United States. SSPE is characterized by the onset of behavioral and intellectual deterioration and seizures years after an acute infection.
In children with lymphoid malignant diseases, delayed-acute measles encephalitis may develop 1 - 6 months after the acute infection and is generally fatal.
Rare complications of measles can range from mild to severe and may include:
The complications of measles in the pregnant mother include:
The diagnosis of measles is usually determined from the classic clinical picture, including the classic triad of cough, coryza, and conjunctivitis, pathognomonic Koplik spots and the characteristic cephalocaudal progression of the morbilliform exanthem.
Other diagnoses to be considered include the following:
Although the diagnosis of measles is usually determined from the classic clinical picture, laboratory identification and confirmation of the diagnosis are necessary for public health and outbreak control.
Laboratory confirmation is achieved by means of the following:
2. Isolation of the Virus (Viral Cultures)
Throat swabs and nasal swabs can be sent on viral transport medium or a viral culturette swab to isolate the measles virus.
Urine specimens can be sent in a sterile container for viral culture.
Viral genotyping in a reference laboratory may determine whether an isolate is endemic or imported.
In immunocompromised individuals, who may have poor antibody responses that preclude serologic confirmation of measles, isolation of the virus from infected tissue or identification of measles antigen by means of immunofluorescence may be the only feasible method of confirming the diagnosis.
3. Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Evaluation
RT-PCR evaluation is highly sensitive at visualizing measles virus RNA and can rapidly confirm the diagnosis in blood, throat, nasopharyngeal, or urine specimens.
The samples should be collected upon first contact with a suspected case of measles when the serum sample for diagnosis is drawn.
Measles-specific IgM titers (Immunoglobulin M): The measles virus sandwich-capture IgM antibody assay, offered through many local health departments and through the CDC, is the quickest method of confirming acute measles. Because IgM may not be detectable during the first 2 days of the rash, blood specimens for measles-specific IgM titers should be drawn on the third day of the rash or on any subsequent day up to 1 month after the onset of the rash to avoid a false-negative IgM result.
Among individuals with a confirmed measles infection, the seropositivity rate for first blood samples is about 77% when collected within 72 hours of rash onset. The seropositivity rate rises to 100% when collected 4 - 11 days after the rash onset. Although the measles serum IgM level remains positive 30 - 60 days after the illness in most individuals, the IgM titer may become undetectable in some individuals at 4 weeks after rash onset. False-positive results can occur in individuals with rheumatologic diseases, parvovirus B19 infection, or infectious mononucleosis.
Measles-specific IgG titers (Immunoglobulin G): Laboratories can confirm measles by demonstrating more than a 4-fold rise in IgG antibodies between acute and convalescent sera, although relying solely on rising IgG titers for the diagnosis delays treatment considerably. The earlier the acute serum is drawn, the more reliable the results. IgG antibodies may be detectable 4 days after the onset of the rash, although most cases have detectable IgG antibodies by about a week after rash onset.
Accordingly, it is recommended that blood serum be drawn on the seventh day after the onset of the rash. Blood drawn for convalescent serum should be drawn 10 - 14 days after that drawn for acute serum, and the acute and convalescent sera should be tested simultaneously as paired sera.
Individuals with subacute sclerosing panencephalitis (SSPE) have unusually high titers of measles antibody in their serum and cerebrospinal fluid (CSF). The earliest confirmation of measles using IgG antibodies takes about 3 weeks from the onset of the illness, a delay too long to permit implementation of effective outbreak control measures.
In atypical measles, laboratory evaluation of serum/blood reveals very low titers of measles antibody early in the course of the disease, followed by extremely high measles IgG antibody titers (e.g. 1:1,000,000).
IgG levels can be explained by current infection, immunity due to past infection or vaccination, or maternal antibodies present in infants younger than 15 months.
Blood for serologic testing can be collected by venipuncture or by finger/heel stick in tubes without additives - either a plain, red-top tube or a serum separator tube. The preferred volume for IgM and/or IgG testing at the CDC is 0.5 – 1.0 ml of serum but testing can be done with as little as 0.1 ml if necessary.
Throat swabs and nasal swabs can be sent on viral transport medium or a viral culturette swab to isolate the measles virus.
Urine specimens can be sent in a sterile container for viral culture.
Viral genotyping in a reference laboratory may determine whether an isolate is endemic or imported.
In immunocompromised individuals, who may have poor antibody responses that preclude serologic confirmation of measles, isolation of the virus from infected tissue or identification of measles antigen by means of immunofluorescence may be the only feasible method of confirming the diagnosis.
RT-PCR evaluation is highly sensitive at visualizing measles virus RNA and can rapidly confirm the diagnosis in blood, throat, nasopharyngeal, or urine specimens. The samples should be collected upon first contact with a suspected case of measles when the serum sample for diagnosis is drawn.
Blood Specimens: A complete blood cell count (CBC) may reveal leukopenia with a relative lymphocytosis and thrombocytopenia. Liver function test (LFT) results may reveal elevated transaminase levels in individuals with measles hepatitis.
Chest Radiography: If bacterial pneumonia is suspected, a chest X-ray should be taken. The frequent occurrence of measles pneumonia, even in uncomplicated cases, limits the predictive value of chest radiography for bacterial bronchopneumonia.
Lumbar Puncture: If encephalitis is suspected, a lumbar puncture should be performed. CSF examination may reveal:
Tissue Analysis and Histologic Findings: A skin biopsy from a lesion of the morbilliform eruption may show spongiosis and vesiculation in the epidermis with scattered dyskeratotic keratinocytes. Occasional lymphoid multinucleated giant cells (≤ 100 nm in diameter) can be identified in biopsies of Koplik spots, in dermal or epithelial rashes, in hair follicles and acrosyringium and in lung or lymphoid tissue. These findings are not specific, but they are suggestive of a viral exanthem. Brain biopsies of individuals with measles encephalitis can reveal demyelination, vascular cuffing, gliosis, and infiltration of fat-laden macrophages near blood vessel walls.
There is no specific antiviral therapy for measles. Medical care is primarily supportive in nature and focused on relieving symptoms and treating complications such as bacterial infections.
Supportive care in the treatment of measles is as follows:
Hospitalization may be indicated for the treatment of measles complications (e.g. bacterial superinfection, pneumonia, dehydration, croup etc.). Individuals with severe complicating infections (e.g. encephalomyelitis) should be admitted for observation and antibiotics given, as appropriate, to their clinical condition.
Individuals should receive regular follow-up care with a primary care physician for surveillance of complications which may arise from the measles infection.
Airborne precautions are indicated for:
In healthcare settings, healthcare providers should follow respiratory etiquette and airborne precautions. Regardless of presumptive immunity status, all healthcare staff entering the room should use respiratory protection consistent with airborne infection control precautions (use of an N95 respirator or a respirator with similar effectiveness in preventing airborne transmission). Because of the possibility, albeit low, of MMR vaccine failure in healthcare staff exposed to infected individuals, they should all observe airborne precautions in caring for individuals with measles. The preferred placement for individuals who require airborne precautions is in a single-patient airborne infection isolation room (AIIR).
Healthcare providers without evidence of immunity who have been exempted from measles vaccination for medical, religious, or other reasons and who do not receive appropriate PEP within the appropriate timeframe should be excluded from affected institutions in the outbreak area until 21 days after the onset of rash in the last case of measles.
Medications used in the prevention or treatment of measles include measles virus vaccines, human immunoglobulin (IG), vitamin A and antivirals (e.g. ribavirin).
The following measles vaccines are available throughout the world:
The measles, mumps and rubella vaccine (M-M-R II) (MMR)
Live measles, mumps, rubella, and varicella virus vaccine (ProQuad) (MMRV)
All adults in the following risk categories should get a second dose of MMR vaccine:
Immunization in Pregnancy
12 Months or Older with HIV Infection
Post-exposure Prophylaxis with the MMR Vaccine
Dosage of the MMR vaccine varies by age. Be aware of potential drug interactions and adverse effects, cautions and contraindications in usage, and precautions when used during pregnancy and lactation.
Since birth before 1957 is not a guarantee of measles immunity, healthcare facilities should consider vaccination of unimmunized healthcare personnel who lack laboratory evidence of immunity who were born before 1957.
Healthcare personnel should have documentation against measles, according to the recommendations of the Advisory Committee on Immunization Practices.
Healthcare personnel without evidence of immunity should get two doses of MMR vaccine, separated by at least 28 days.
If a healthcare worker without evidence of immunity is exposed to measles, the MMR vaccine should be given within 72 hours of exposure.
Healthcare personnel without evidence of immunity should be excluded from duty from day 5 after the first exposure to day 21 after the last exposure regardless of post-exposure MMR vaccine.
Contraindications to the MMR vaccine include:
Precautions to the MMR vaccine include:
Individuals may be vaccinated who are:
This is a live vaccine that induces active immunity against viruses that cause measles, mumps, rubella, and varicella (Chickenpox).
Contraindications to the MMRV vaccine include:
Children should not get the MMRV vaccine if they:
Precautions to the MMRV vaccine include:
Early findings from an ongoing CDC study show that children who get an MMRV vaccine may be twice more likely to have a febrile seizure 7 - 10 days after getting the vaccine than children who get MMR and varicella vaccines (by 2 separate injections) at the same healthcare visit.
Children may also get these vaccines as two separate shots: MMR (measles, mumps, rubella) and varicella vaccines. The essential question remains: 1 Shot (MMRV) or 2 Shots (MMR and Varicella)?
Human Immunoglobulin (IG) prevents or modifies the measles virus in susceptible contacts if administered within 6 days of exposure. Post-exposure prophylaxis should be considered in unvaccinated contacts. Timely tracing of contacts should be a priority. These individuals should receive regular follow-up care with a primary care physician for surveillance of complications arising from the infection.
Intramuscular IG (IGIM) is a transient source of IG. Pooled human immune globulins from donors are pharmacologically used as replacement therapy for primary and secondary immunodeficiencies, and IGG antibodies against viral, bacteria, parasitic, and mycoplasma antigens. These pooled human immune globulins also provide passive immunity through an increase in antibody titer and antigen-antibody reaction potential.
Post-exposure prophylaxis with human immunoglobulin (IG) should be administered to individuals who are at risk for severe illness and complications from measles, such as infants younger than 12 months of age, pregnant women without evidence of measles immunity, and individuals with severely compromised immune systems.
IG should not be used to control measles outbreaks, but rather to reduce the risk for infection and complications in the individuals receiving it. IGIM can be given to other individuals who do not have evidence of immunity against measles, but priority should be given to individuals exposed in settings with intense, prolonged, close contact, such as a households, daycare settings, or classrooms where the risk of transmission is highest.
After receipt of IG, individuals who have been exposed to the measles virus cannot return to work in healthcare settings. In other settings, such as childcare, school, or work, factors such as immune status, intense or prolonged contact, and presence of populations at risk, should be taken into consideration before allowing individuals who have been exposed to return. These factors may decrease the effectiveness of IG or increase the risk of disease and complications depending on the setting to which they are returning.
If a healthcare worker without evidence of immunity is exposed to measles, the MMR vaccine should be given within 72 hours, or IG should be given within 6 days of exposure. All healthcare personnel without evidence of immunity should be excluded from duty from day 5 after first exposure to day 21 after last exposure, regardless of post-exposure prophylaxis.
Human immunoglobulin administration varies by age, dosage based on individuals’ clinical response and serum IgG trough levels, route of administration, potential drug interactions, potential adverse effects, contraindications and cautions, pregnancy and lactation status.
Human immunoglobulin can be found under such brand names as: Bivigam, Carimune, Flebogamma, GamaSTAN, Gamunex-C, Gammagard, Hizentra, HyQvia, and Privigen.
It is indicated for all contacts of individuals with measles who have no evidence of immunity against measles and who:
Contraindications to Human Immunoglobulin (IG) include:
Precautions to Human Immunoglobulin (IG) include:
Vitamin A supplementation has been associated with an approximately 50% reduction in morbidity and mortality and appears to help prevent eye damage and blindness.
Because Vitamin A deficiency is associated with severe disease from measles, the WHO recommends all children diagnosed with measles should receive vitamin A supplementation regardless of their country of residence, based on their age, as follows:
Vitamin A supplementation plays a role in embryonic development, visual adaptation to darkness, immune function, and maintenance of epithelial cells. Vitamin A is a fat-soluble vitamin needed for growth of skin, bones, and male and female reproductive organs. Vitamin A can be found in liver, butter, eggs, green leafy vegetables, colorful fruits and vegetables such as carrots, mango, pumpkin and sweet potatoes.
Vitamin A supplementation varies by age, dosage recommendations, route of administration, potential drug interactions, potential adverse effects, contraindications and cautions, pregnancy and lactation status.
Vitamin A supplementation can be found under such names as: Retinol, Aquasol A, Vitamin A, retinyl acetate, retinyl palmitate, A-25, Gordons-Vite A.
Vitamin A supplementation is indicated for all individuals with measles who are:
Vitamin A deficient whether children or adults.
Children with acute measles regardless of their country of residence due to the reduction in morbidity and mortality rates (WHO recommendation).
United States children with severe measles who have low serum concentrations of vitamin A. Thus, two doses of vitamin A given 24 hours apart are recommended. A third age-specific dose should be given 2 to 4 weeks later to children with clinical signs and symptoms of vitamin A deficiency.
Contraindications to Vitamin A supplementation include:
Precautions to Vitamin A supplementation include:
Ribavirin, a guanosine analogue, is for experimental use only. Its mechanism of action is not fully defined but it may inhibit the initiation and elongation of RNA fragments by inhibiting polymerase activity, which in turn results in the inhibition of viral protein synthesis.
The measles virus is susceptible to ribavirin in vitro. Although ribavirin (either IV or aerosolized) has been used to treat severely affected and immunocompromised individuals with acute measles or subacute sclerosing panencephalitis (SSPE), no controlled trials have been conducted.
Ribavirin dosage varies by age, route of administration, potential drug interactions, potential adverse effects, cautions and contraindications, pregnancy and lactation precautions and toxicity.
Antiviral therapy can be found under such brand names as Ribavirin, Moderiba, Virazole, Rebetol, Ribasphere, RibaPak, and Copegus.
Ribavirin is not approved by the United States Food and Drug Administration (FDA) for any indication, and such use should be considered experimental.
Contraindications to antiviral therapy include:
Black Box Warnings
Contraindications to antiviral therapy include:
Precautions to antiviral therapy include:
Because the transmission of wild-type measles has been interrupted in the United States and all recent epidemics in the United States have been linked to imported cases, immediately reporting any suspected case of measles to a local or state health department is imperative. Obtaining serum for IgM antibody testing as soon as possible (i.e. on or after the third day of rash) is a priority.
The Centers for Disease Control and Prevention (CDC) clinical case definition for reporting purposes requires only the following:
Further, for reporting purposes for the CDC, cases are classified as follows:
State and local health departments have the lead in investigating measles cases and outbreaks when they occur. The CDC helps and supports health departments in these investigations by:
In order to maintain reference stocks of viruses and provide facilities capable of conducting viral sequencing, two global Measles Strain Banks have been established. The Measles, Mumps, Rubella and Herpesvirus Laboratory Branch of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA, and Health Protection Agency (HPA) in London, UK, were selected to serve this purpose. The Health Protection Agency in London, UK, contains sequence information from more than 10,000 measles samples.
The Measles Nucleotide Surveillance (MeaNS) initiative was developed as a web-accessible and quality-controlled nucleotide database for the WHO Measles Laboratory Network. This database is used as a tool to track measles sequence diversity and monitor elimination of virus strains. Full access to MeaNS is given only to members of the WHO Measles and Rubella Laboratory Network (LabNet). Upon request, viral sequencing and analysis can be provided for measles virus characterization as well as storage of viral strains. Sequences submitted to MeaNS are automatically submitted to the WHO Global Measles Genotype Database at the WHO Headquarters in Geneva. Sequences can also be submitted to GenBank. Measles sequences in GenBank are imported into MeaNS on a bi-weekly basis.
The prognosis for measles is generally good with the majority of individuals surviving the infection. The measles infection only occasionally is fatal. The CDC reports that the childhood mortality rate from measles infection in the United States is 0.1 - 0.2%. However, many complications and sequelae may develop. Measles remains a major cause of childhood blindness in developing countries.
Globally, measles remains one of the leading causes of death in young children. According to the CDC, measles caused an estimated 197,000 deaths worldwide in 2007. An estimated 85% of these deaths occurred in Africa and Southeast Asia. From 2000 - 2007, deaths worldwide fell by 74% (to 197,000 from an estimated 750,000), thanks to the partnership of several global organizations.
Case-fatality rates are higher among children younger than 5 years of age. The highest fatality rates are among infants 4 - 12 months of age and in children who are immunocompromised because of human immunodeficiency virus (HIV) infection or other causes.
Complications of measles are more likely to occur in individuals younger than 5 years or older than 20 years of age. Morbidity and mortality are increased in individuals with immune deficiency disorders, malnutrition, vitamin A deficiency, and inadequate vaccination.
Thus, prevention remains a global priority. Early diagnosis and treatment affects the outcome in all age groups and reduces the morbidity and mortality from the complications of measles.
Unsubstantiated claims that suggest an association between the measles vaccine and autism have resulted in reduced vaccine use and contributed to a recent resurgence of measles in countries where immunization rates have fallen to below the level needed to maintain herd immunity.
Considering that for industrialized countries such as the United States, endemic transmission of measles may be reestablished if measles immunity falls to less than 93 - 95%, efforts to ensure high immunization rates among individuals in both developed and developing countries must be sustained.
So the essential question remains….Are you willing to risk your health or the health of your loved ones including children for philosophical, legal, religious or personal beliefs, as well as, indirectly the health and well-being of your entire community by not choosing to prevent a disease which is so easily preventable?
American Academy of Pediatrics. Measles. In: Pickering LK, ed. Red Book: Report of the Committee on Infectious Disease. Elk Grove, Ill: AAP; 2006:441-52.
Anlar B (2013). "Subacute sclerosing panencephalitis and chronic viral encephalitis". Handbook of Clinical Neurology 112: 1183–1189. doi:10.1016/B978-0-444-52910-7.00039-8. PMID 23622327.
Atkinson, William (2011). Epidemiology and Prevention of Vaccine-Preventable Diseases (12 ed.). Public Health Foundation. pp. 301–323. ISBN 9780983263135. Retrieved 5 February 2015.
Barrero PR, Grippo J, Viegas M, Mistchenko AS. Wild-type Measles Virus in Brain Tissue of Children with Subacute Sclerosing Panencephalitis, Argentina. Emerg Infect Dis. 2003; 9:1333-1336.
Bartlett, M.S. (1957). "Measles periodicity and community size". J. Roy. Stat. Soc. Ser. A (120): 48–70.
Bar-On S, Ochshorn Y, Halutz O, Aboudy Y, Many A. Detection of measles virus by reverse-transcriptase polymerase chain reaction in a placenta. J Matern Fetal Neonatal Med. Aug 2010;23(8):935-7. [Medline].
Baxby D (1997). "Classic Paper: Henry Koplik. The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal membrane". Reviews in Medical Virology 7 (2): 71–4. doi:10.1002/(SICI)1099-1654(199707)7:2<71::AID-RMV185>3.0.CO;2-S. PMID 10398471.
Bellini WJ, Rota JS, Lowe LE, et al. Subacute sclerosing panencephalitis: more cases of this fatal disease are prevented by measles immunization than was previously recognized. J Infect Dis 2005;192:1686--93.
Benkimoun P. Outbreak of measles in France shows no signs of abating. BMJ. May 20 2011;342:d3161. [Medline].
Biesbroeck L, Sidbury R (November 2013). "Viral exanthems: an update". Dermatologic therapy 26 (6): 433–8. doi:10.1111/dth.12107. PMID 24552405.
Black, Francis L. (July 1966). "Measles endemicity in insular populations: Critical community size and its evolutionary implication". Journal of Theoretical Biology 11 (2): 207–211. doi:10.1016/0022-5193(66)90161-5. ISSN 0022-5193. PMID 5965486. Retrieved 2014-10-15.
Bonthius DJ, Stanek N, Grose C. Subacute Sclerosing Panencephalitis, a Measles Complication, in an Internationally Adopted Child. Emerg Infect Dis. 2000. 6:377-381.
"Bug of the Month - Measles". Banner Gateway Medical Center. April 2012. Retrieved May 3, 2013.
Byrne, Joseph Patrick (2008). Encyclopedia of Pestilence, Pandemics, and Plagues: A–M. ABC-CLIO. p. 413. ISBN 0-313-34102-8.
California Department of Public Health Confirms 59 Cases of Measles. California Department of Public Health. (Visit Website). Accessed January 23, 2015.
Campbell H, Andrews N, Brown KE and Miller E. Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol. 2007;36:1334-1348.
Caserta, MT, ed. (September 2013). "Measles". Merck Manual Professional. Merck Sharp & Dohme Corp. Retrieved 23 March 2014.
Casteels-Van Daele M, Van Geet C, Wouters C, Eggermont E (April 2000). "Reye syndrome revisited: a descriptive term covering a group of heterogeneous disorders". European Journal of Pediatrics 159 (9): 641–8. doi:10.1007/PL00008399. PMID 11014461. Retrieved 2011-03-17.
CDC. Subacute Sclerosing Panencephalitis Surveillance - United States. MMWR. 1982. 31:585-8.
CDC. Measles - United States, January - May 20, 2011. MMWR Morb Mortal Wkly Rep. 2011 May 24;60(Early Release):1-4.
CDC. U.S. multi-state measles outbreak, December 2014 - January 2015. Atlanta, GA: US Department of Health and Human Services, CDC; 2015. (Visit Website).
CDC. Summary of notifiable diseases - United States, 2008. MMWR 2010;57(54).
CDC. Summary of notifiable diseases - United States, 2011. MMWR 2013;60(53).
CDC. Notes from the field: measles outbreak among members of a religious community - Brooklyn, New York, March–June 2013. MMWR 2013;62:752–3.
CDC. Documentation and verification of measles, rubella, and congenital rubella syndrome elimination in the Region of the Americas. Atlanta, GA: US Department of Health and Human Services, CDC; 2012. (Visit Website).
CDC. Notes from the field: measles outbreak associated with a traveler returning from India - North Carolina. MMWR 2013;62:753.
CDC. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2013;62(No. RR-4).
CDC. 2007 guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. Atlanta, GA: US Department of Health and Human Services, CDC; 2007. Available at http://www.cdc.gov/hicpac/2007ip/2007isolationprecautions.html.
CDC. National, state, and local area vaccination coverage among children aged 19–35 months - United States, 2012. MMWR 2013;62:733–40.
CDC. Program in brief: Measles Mortality Reduction and Regional Global Measles Elimination. Available at http://www.cdc.gov/ncird/progbriefs/downloads/global-measles-elim.pdf. Accessed April 14, 2009.
CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases. Chapter 10, Measles. 8th Edition, 2004.
CDC. Manual for the surveillance of vaccine-preventable diseases. 4th ed. Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/vaccines/pubs/surv-manual/default.htm. Accessed May 20, 2011.
CDC. Manual for the surveillance of vaccine-preventable diseases. Chapter 7: measles. Atlanta, GA: US Department of Health and Human Services, CDC; 2013. Available at http://www.cdc.gov/vaccines/pubs/surv-manual/chpt07-measles.pdf .
CDC. Measles - United States, January 1 - April 25, 2008. MMWR 2008;57:494-8.
CDC. Measles outbreak - Hennepin County, Minnesota, February--March 2011. MMWR 2011;60:421.
CDC. Measles, mumps and rubella-vaccine use and strategies for elimination of measles, rubella and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1998;47(No. RR-8).
Chen S.S.P. (October 3, 2011). Measles (Report). Medscape.
Cohen BE, Durstenfeld A, Roehm PC (July 2014). "Viral causes of hearing loss: a review for hearing health professionals". Trends in Hearing 18: 2331216514541361. doi:10.1177/2331216514541361. PMC 4222184. PMID 25080364.
Coleman KP, Markey PG. Measles transmission in immunized and partially immunized air travellers. Epidemiol Infect. Jul 2010;138(7):1012-5. [Medline].
"Complications of measles". CDC. November 3, 2014. Retrieved November 7, 2014.
Conn's Current Therapy 2015: Expert Consult - Online. Elsevier Health Sciences. 2014. p. Council of State and Territorial Epidemiologists. List of nationally notifiable conditions. Atlanta, GA: Council of State and Territorial Epidemiologists; 2012. (Visit Website). ISBN 9780323319560.
Dayan GH, Ortega-Sanchez IR, LeBaron CW, Quinlisk MP, Iowa Measles Response Team. The cost of containing one case of measles: the economic impact on the public health infrastructure - Iowa, 2004. Pediatrics 2005;116:e1--e4
D'Souza RM, D'Souza R (2002). "Vitamin A for treating measles in children". The Cochrane Database of Systematic Reviews (1): CD001479. doi:10.1002/14651858.CD001479. PMID 11869601.
D'Souza RM, D'Souza R (April 2002). "Vitamin A for preventing secondary infections in children with measles - a systematic review". Journal of Tropical Pediatrics 48 (2): 72–7. doi:10.1093/tropej/48.2.72. PMID 12022432.
Durrheim DN, Kelly H, Ferson MJ, Featherstone D (August 2007). "Remaining measles challenges in Australia". The Medical journal of Australia 187 (3): 181–4. PMID 17680748.
Editorial team. Measles once again endemic in the United Kingdom. Eurosurveillance 2008;13. (Visit Website). Accessed May 20, 2011.
Ellison, J.B (1931). "Pneumonia in Measles". 1931 Archives of Disease in Childhood 6 (31). pp. 37–52. PMC 1975146.
Enders JF, Peebles TC (1954). "Propagation in tissue culture of cytopathogenic agents from patients with measles". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 86 (2): 277–86. doi:10.3181/00379727-86-21073. PMID 13177653.
EuroSurveillance Editorial Team. Measles once again endemic in the United Kingdom. Eurosurveillance 2008;13:1. (Visit Website).
Fiebelkorn AP, Redd SB, Gallagher K, et al. Measles in the United States during the Postelimination Era. J Infect Dis 2010; 202:1520-8.
Filia A, De Crescenzo M, Seyler T, et al. Measles resurges in Italy: preliminary data from September 2007 to May 2008. Eurosurveillance 2008;13:pii=18928. (Visit Website).
Fisher DL, Defres S, Solomon T (2014). "Measles-induced encephalitis". QJM. Epub ahead of print: 177–182. doi:10.1093/qjmed/hcu113. PMID 24865261. Retrieved August 27, 2014.
Missing or empty |url= (help)
Forni AL, Schluger NW, Roberts RB. Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous. Clin Infect Dis Sep. 1994;19(3):454-62. [Medline].
Friedman M, Hadari I, Goldstein V, Sarov I (1983). "Virus-specific secretory IgA antibodies as a means of rapid diagnosis of measles and mumps infection". Israel Journal of Medical Sciences 19 (10): 881–884. PMID 6662670.
Furuse, Yuki; Akira Suzuki; Hitoshi Oshitani (2010-03-04). "Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries". Virology Journal 7: 52. doi:10.1186/1743-422X-7-52. ISSN 1743-422X. PMC 2838858. PMID 20202190. Retrieved 2014-09-14.
Fusilli G, De Mitri B. Acute pancreatitis associated with the measles virus: case report and review of literature data. Pancreas. May 2009;38(4):478-80. [Medline].
Galindo BM, Concepción D, Galindo MA, Pérez A, Saiz J (2012). "Vaccine-related adverse events in Cuban children, 1999–2008". MEDICC Review 14 (1): 38–43. PMID 22334111.
Gardiner, W. T. (2007). "Otitis Media in Measles". The Journal of Laryngology & Otology 39 (11): 614–617. doi:10.1017/S0022215100026712.
Garenne M. Sex differences in measles mortality: a world review. Int J Epidemiol. Jun 1994;23(3):632-42. [Medline].
Gastañaduy PA, Redd SB, Fiebelkorn AP, Rota JS, Rota PA, Bellini WJ, et al. Measles - United States, January 1-May 23, 2014. MMWR Morb Mortal Wkly Rep. Jun 6 2014;63(22):496-499. [Medline].
Gay NJ. The theory of measles elimination: implications for the design of elimination strategies. J Infect Dis 2004;189(Suppl1)S27--35.
GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.". Lancet 385: 117–171. doi:10.1016/S0140-6736(14)61682-2. PMC 4340604. PMID 25530442.
Gindler J, Tinker S, Markowitz L, et al. Acute measles mortality in the United States, 1987--2002. J Infect Dis 2004;189(Suppl 1):S69--77.
Global measles mortality, 2000-2008. MMWR Morb Mortal Wkly Rep. Dec 4 2009;58(47):1321-6. [Medline].
Global distribution of measles and rubella genotypes- update
WHO/Wkly Epi Rec December 15 2006; 81:474-479.
Global measles and rubella laboratory network- update
WHO/Wkly Epi Rec November 4 2005; 80:384-388.
Gowda VK, Sukanya V (2012). "Acquired Immunodeficiency Syndrome with Subacute Sclerosing Panencephalitis". Pediatric Neurology 47 (5): 379–381. doi:10.1016/j.pediatrneurol.2012.06.020. PMID 23044024.
[Guideline] American Academy of Pediatrics; Committee on Infectious Diseases. Policy Statement--Prevention of Varicella: Update of Recommendations for Use of Quadrivalent and Monovalent Varicella Vaccines in Children. Pediatrics. Aug 28 2011;[Medline].
[Guideline] Centers for Disease Control and Prevention. Recommended immunization schedules for persons aged 0 through 18 years - United States, 2009. CDC Recommended Vaccine Schedule. Dec 2008; 57(51;52):[Full Text].
[Guideline] Marin M, Broder KR, Temte JL, Snider DE, Seward JF. Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. May 7 2010; 59:1-12. [Medline]. [Full Text].
Hand L. MMR: ACIP Vaccine Recommendations, Japan Rubella Outbreak. (Visit Website). Accessed July 15, 2013.
Harpaz R, Papania MJ, McCauley MM, Redd SB. Has surveillance been adequate to detect endemic measles in the United States? J Infect Dis 2004;189:(Suppl 1):S191–5.
Harrison L. AAP updates measles recommendations. Medscape Medical News. WebMD Inc. (Visit Website). Accessed March 31, 2015.
Helfand RF, Heath JL, Anderson LJ, et al. Diagnosis of measles with an IgM capture EIA: the optimal timing of specimen collection after rash onset. J Infect Dis. Jan 1997;175(1):195-9. [Medline].
Helfand RF, Witte D, Fowlkes A, Garcia P, Yang C, Fudzulani R, Walls L, Bae S, Strebel P, Broadhead R, Bellini WJ, Cutts F (2008). "Evaluation of the immune response to a 2-dose measles vaccination schedule administered at 6 and 9 months of age to HIV-infected and HIV-uninfected children in Malawi". The Journal of Infectious Diseases 198 (10): 1457–65. doi:10.1086/592756. PMID 18828743.
Henderson D. Measles vaccine: lower seizure risk when given early on. Medscape Medical News [serial online]. October 14, 2013;Accessed October 21, 2013. (Visit Website).
Hosoya M, Shigeta S, Mori S, et al. High-dose intravenous ribavirin therapy for subacute sclerosing panencephalitis. Antimicrob Agents Chemother. Mar 2001;45(3):943-5. [Medline].
Huiming Y, Chaomin W, Meng M (2005). Yang, Huiming, ed. "Vitamin A for treating measles in children". The Cochrane Database of Systematic Reviews (4): CD001479. doi:10.1002/14651858.CD001479.pub3. PMID 16235283.
Hviid A. Measles-mumps-rubella-varicella combination vaccine increases risk of febrile seizure. J Pediatr. Jan 2011;158(1):170. [Medline]. [Full Text].
Immunization Schedules. Updated August 25, 2010. CDC. Available at http://www.cdc.gov/vaccines/recs/schedules/default.htm. Accessed May 25, 2011.
Jin L, Beard S, Brown DWG, Miller E. Characterization of Measles Virus Strains Causing SSPE: A Study of 11 Cases. J of Neurovirol. 2002; 8:335-344.
Kabra, SK; Lodhra, R (14 August 2013). "Antibiotics for preventing complications in children with measles". Cochrane Database of Systematic Reviews 8: CD001477. doi:10.1002/14651858.CD001477.pub4. PMID 23943263.
Katz SL, Hinman AR. Summary and conclusions: measles elimination meeting, 16 - 17 March 2000. J Infect Dis 2004;189(Suppl 1):S43--7.
Klein NP, Fireman B, Yih WK, Lewis E, Kulldorff M, Ray P, et al. Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures. Pediatrics. Jul 2010;126(1):e1-8. [Medline].
Leuridan E, Sabbe M, Van Damme P (September 2012). "Measles outbreak in Europe: susceptibility of infants too young to be immunized". Vaccine 30 (41): 5905–13. doi:10.1016/j.vaccine.2012.07.035. PMID 22841972.
Lowes R. Three-Fold Increase in Measles Warrants Vigilance, CDC Says. Medscape Medical News. (Visit Website). Accessed December 9, 2013.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY et al. (Dec 15, 2012). "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet 380 (9859): 2095–128. doi:10.1016/S0140-6736(12)61728-0. PMID 23245604. CS1 maint: Explicit use of et al. (link)
Ludlow M, McQuaid S, Milner D, de Swart RL, Duprex WP (January 2015). "Pathological consequences of systemic measles virus infection". The Journal of Pathology 235 (2): 253–65. doi:10.1002/path.4457. PMID 25294240.
Macdonald S (2002). "Aspirin use to be banned in under 16 year olds". BMJ (Clinical Research Ed.) 325 (7371): 988. doi:10.1136/bmj.325.7371.988/c. PMC 1169585. PMID 12411346. "Aspirin and Reye's Syndrome". MHRA. October 2003. Retrieved 2011-03-17.
Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. Nov 7 2002;347(19):1477-82. [Medline].
Markowitz LE, Preblud SR, Fine PE, Orenstein WA. Duration of live measles vaccine-induced immunity. Pediatr Infect Dis J. Feb 1990;9(2):101-10. [Medline].
McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2013;62(No. RR-4):1–34.
Measles--United States, 2005. MMWR Morb Mortal Wkly Rep. Dec 22 2006;55(50):1348-51. [Medline].
"Measles vaccines: WHO position paper." (PDF). Weekly epidemiological record 84 (35): 349–60. 28 August 2009. PMID 19714924.
"Measles (Red Measles, Rubeola)". (Visit Website). Retrieved 10 February 2015.
"Measles (Rubeola) Signs and Symptoms". cdc.gov. November 3, 2014. Retrieved 5 February 2015.
"Measles Fact sheet N°286". Who.Int. November 2014. Retrieved 4 February 2015.
Measles Surveillance Data after WHO, last updated 2014-3-6
Measles reported cases by WHO in 2014
Measles hits rare Andaman tribe. BBC News. May 16, 2006.
"Measles Prevention: Recommendations of the Immunization Practices Advisory Committee (ACIP)". Centers for Disease Control and Prevention (CDC).
Measles, World Health Organization Fact sheet N°286. Retrieved June 28, 2012. Updated February 2014.
Measles outbreaks and progress toward measles preelimination - African region, 2009-2010. MMWR Morb Mortal Wkly Rep. Apr 1 2011;60(12):374-8. [Medline].
Measles imported by returning U.S. travelers aged 6-23 months, 2001-2011. MMWR Morb Mortal Wkly Rep. Apr 8 2011;60(13):397-400. [Medline].
Measles Initiative highlights the importance of adherence to global goals and strategies (news release). (Visit Website). Accessed May 26, 2011.
Meissner HC, Strebel PM, Orenstein WA. Measles vaccines and the potential for worldwide eradication of measles. Pediatrics. 2004;114(4):1065-9. [Medline]. [Full Text].
Miller C, Farrington CP, Harbert K. The Epidemiology of Subacute Sclerosing Panencephalitis in England and Wales 1970-1989. Int J Epidemiol. 1992; 21:998-1006.
MMR-II vaccine insert. (Visit Website).
Mrozek-Budzyn D, Kieltyka A, Majewska R. Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study. Pediatr Infect Dis J. May 2010;29(5):397-400. [Medline].
National Institutes of Health Office of Dietary Supplements (2013). "Vitamin A". U.S. Department of Health & Human Services. Retrieved 11 March 2015.
New genotype of measles virus and update on global distribution of measles genotypes
WHO/Wkly Epi Rec October 7 2005; 80:347-351.
NHS UK: Symptoms of measles. Last reviewed: 26/01/2010.
Nomenclature for describing the genetic characteristics of wild-type measles viruses
WHO/Wkly Epi Rec August 10 2001; 76:242-247.
Nomenclature for describing the genetic characteristics of wild-type measles viruses
WHO/Wkly Epi Rec August 17 2001; 76:249-251.
Notes from the field: Measles outbreak - Hennepin County, Minnesota, February-March 2011. MMWR Morb Mortal Wkly Rep. Apr 8 2011;60(13):421. [Medline].
Noyce RS, Richardson CD (September 2012). "Nectin 4 is the epithelial cell receptor for measles virus". Trends in Microbiology 20 (9): 429–39. doi:10.1016/j.tim.2012.05.006. PMID 22721863.
Offit PA (2007). Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases. Washington, DC: Smithsonian. ISBN 0-06-122796-X.
Oldakowska A, Marczynska M (2008). "Measles vaccination in HIV infected children". Medycyna Wieku Rozwojowego 12 (2 Pt 2): 675–680. PMID 19418943.
Omer SB, Pan WKY, Halsey NA, et al. Nonmedical exemptions to school immunization requirements: secular trends and association of state policies with pertussis incidence. JAMA 2006;296:1757--63.
Omer SB, Salmon DA, Orenstein WA, deHart MP, Halsey N. Vaccine refusal, mandatory immunization, and the risks of vaccine-preventable diseases. N Engl J Med 2009;360:1981–8
Orenstein WA, Papania MJ, Wharton ME. Measles elimination in the United States. J Infect Dis. May 1 2004;189 Suppl 1:S1-3. [Medline].
Papania MJ, Wallace GS, Rota PA, Icenogle JP, Fiebelkorn AP, Armstrong GL, et al. Elimination of Endemic Measles, Rubella, and Congenital Rubella Syndrome From the Western Hemisphere: The US Experience. JAMA Pediatr. Dec 5 2013;[Medline].
Parker AA, Staggs W, Dayan GH, et al. Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. N Engl J Med 2006;355:447--55.
Parker Fiebelkorn A, Redd SB, Gallagher K, et al. Measles in the United States during the postelimination era. J Infect Dis 2010;202:1520--8.
"Past pandemics that ravaged Europe", BBC News, November 7, 2005
Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis. May 1 2004;189 Suppl 1:S4-16. [Medline].
Prevention of Measles, Rubella, Congenital Rubella Syndrome, and Mumps, 2013: Summary Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. Jun 14 2013;62:1-34. [Medline].
2015 Report of the Committee on Infectious Diseases. Early Release from Red Book. American Academy of Pediatrics. (Visit Website). Accessed March 31, 2015.
Reported vaccine-preventable diseases--United States, 1993, and the childhood immunization initiative. MMWR Morb Mortal Wkly Rep. Feb 4 1994;43(4):57-60. [Medline].
Rima BK, Earle JA, Yeo RP, Herlihy L, Baczko K, ter Meulen V, Carabaña J, Caballero M, Celma ML, Fernandez-Muñoz R (1995). "Temporal and geographical distribution of measles virus genotypes". The Journal of General Virology 76 (5): 1173–80. doi:10.1099/0022-1317-76-5-1173. PMID 7730801.
Rota PA, Brown K, Mankertz A, et al. Global distribution of measles genotypes and measles molecular epidemiology. J Infect Dis 2011;204(Suppl 1):S514–23.
Rowhani-Rahbar A, Fireman B, Lewis E, et al. Effect of age on the risk of fever and seizures following immunization With measles-containing vaccines in children. JAMA Pediatr. Oct 14 2013;[Medline].
Sabella C. Measles: not just a childhood rash. Cleve Clin J Med. Mar 2010;77(3):207-13. [Medline].
Schneider-Schaulies S, Schneider-Schaulies J. Measles virus-induced immunosuppression. Curr Top Microbiol Immunol. 2009;330:243-69. [Medline].
Schrör K (2007). "Aspirin and Reye Syndrome: A Review of the Evidence". Paediatric Drugs 9 (3): 195–204. doi:10.2165/00148581-200709030-00008. PMID 17523700. Retrieved 2011-03-17.
Semba RD, Bloem MW (March 2004). "Measles blindness". Survey of Ophthalmology 49 (2): 243–55. doi:10.1016/j.survophthal.2003.12.005. PMID 14998696.
Sension MG, Quinn TC, Markowitz LE, Linnan MJ, Jones TS, Francis HL, Nzilambi N, Duma MN, Ryder RW (1988). "Measles in hospitalized African children with human immunodeficiency virus". American Journal of Diseases of Children (1960) 142 (12): 1271–2. doi:10.1001/archpedi.1988.02150120025021. PMID 3195521.
Smeeth L, Cook C, Fombonne E, et al. MMR vaccination and pervasive developmental disorders: a case-control study. Lancet. 2004;11-17;364(9438):963-9. [Medline].
Smith PJ, Chu SY, Barker LE. Children who have received no vaccines: who are they and where do they live? Pediatrics 2004;114:187–95.
Specimens for Detection of Measles RNA by RT-PCR or Virus Isolation(Visit Website).
Standardization of the nomenclature for describing the genetic characteristics of wild-type measles viruses WHO/Wkly Epi Rec August 28 1998; 73, 265-269.
Starko KM, Ray CG, Dominguez LB, Stromberg WL, Woodall DF (6 Dec 1980). "Reye's Syndrome and Salicylate Use". Pediatrics 66 (6): 859–64. PMID 7454476. Retrieved 2011-03-17.
"Surgeon General's advisory on the use of salicylates and Reye syndrome". MMWR. Morbidity and Mortality Weekly Report 31 (22): 289–90. June 1982. PMID 6810083.
Themed Entertainment Association, AECOM. Global attractions attendance report. Burbank, CA: Themed Entertainment Association, AECOM; 2014. (Visit Website)
Total Health (May 5, 2010). "Actual Confirmed Measles Cases in UK". totalhealth. Retrieved May 4, 2013.
The Merck Manuals Online Medical Library. (Visit Website).
Torrey EF and Yolken RH. 2005. Their bugs are worse than their bite. Washington Post, April 3, p. B01.
UK Health Protection Agency. Confirmed measles cases in England and Wales---an update to end-May 2008. Health Protection Report 2008;2(25). (Visit Website).
UNICEF (2007). "Global goal to reduce measles deaths in children surpassed". Joint press release. Retrieved 11 March 2015.
Update: measles--United States, January-July 2008. MMWR Morb Mortal Wkly Rep. Aug 22 2008;57(33):893-6. [Medline].
Update of the nomenclature for describing the genetic characteristics of wild-type measles viruses: new genotypes and reference strains
WHO/Wkly Epi Rec July 4 2003; 78:229-232.
Waggoner JJ, Soda EA, Deresinski S (October 2013). "Rare and emerging viral infections in transplant recipients". Clinical infectious diseases 57 (8): 1182–8. doi:10.1093/cid/cit456. PMID 23839998.
Wang E, Clymer J, Davis-Hayes C, Buttenheim A. Nonmedical exemptions from school immunization requirements: a systematic review. Am J Public Health 2014;104:e62–84.
Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1998;47(No. RR-8).
World Health Organization. Global elimination of measles - report by the Secretariate, 16 April 2009. (Visit Website). Accessed May 20, 2011.
WHO: Global summary on measles, 2006
WHO Weekly Epidemiology Record, 4th December 2009 WHO.int
Zipprich J, Winter K, Hacker J, Xia D, Watt J, Harriman K; CDC. Measles outbreak - California, December 2014-February 2015. MMWR Morb Mortal Wkly Rep 2015;64:153–4.