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Measles: How Soon Forgotten

3.00 Contact Hours:
A score of 80% correct answers on a test is required to successfully complete any course and attain a certificate of completion.
Author:    Pamela Downey (MSN, ARNP)

Purpose/Goals

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.

Picture it:

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”.

Objectives

After completing this course, the learner will be able to meet the following objectives:

  1. Describe the epidemiology of measles in the United States and worldwide.

  2. List the modes of transmission of the measles virus.

  3. Relate the evidence which constitutes immunity to the measles virus.

  4. Describe the signs and symptoms of the prodromal, enanthem and exanthem phases of the measles infection.

  5. Relate the goals and interventions used in the management and treatment of the measles infected individual.

  6. Compare and contrast medications used in the prevention or treatment of measles including recommendations and contraindications/precautions.

  7. Relate the prognosis of survival of measles.

Etiology

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.

Genetic Characterization and Sequencing

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

Pathophysiology

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.

Pre-Vaccine Era

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.

Vaccine Development

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.

Measles Elimination

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.

Epidemiology

United States Statistics

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.

  • Cases of measles acquired outside the United States are categorized as importations. Cases are considered imported if exposure to the measles virus occurred outside the United States 7 - 21 days before the onset of the rash and the rash occurred within 21 days of entry into the United States, with no known exposure to measles in the United States during that period.
  • Cases of measles acquired inside the United States are considered importation associated if:
  • The cases are linked epidemiologically via a chain of transmission to an importation or have virologic evidence of importation. Laboratory confirmation involves serologic detection of measles-specific immunoglobulin M, a significant increase in measles immunoglobulin G level, isolation of the measles virus, or detection of the measles virus by nucleic acid amplification in a clinical specimen (e.g., nasopharyngeal or oropharyngeal swab, nasal aspirate, throat wash, or urine).
  • The cases have no epidemiologic link identified but the viral genotype detected suggests recent
  • Other cases are classified as having an unknown source.

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.

2001-2008

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.

2011-2015

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.

Summary

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.

International Statistics

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.

REPORTED CASES OF MEASLES

WHO-Region

1980 1990 2000 2005 2014

African Region

1,240,993

481,204

520,102

316,224

12,125

Region of the Americas

257,790

218,579

1,755

66

3,100

Eastern Mediterranean Region

341,624

59,058

38,592

15,069

2,214

European Region

851,849

234,827

37,421

37,332

2,430

South-East Asia Region

199,535

224,925

61,975

83,627

1,540

Western Pacific Region

1,319,640

155,490

176,493

128,016

34,310

Worldwide

4,211,431

1,374,083

836,338

580,287

55,719

Age-Related Demographics

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.

Sex and Race-Related Demographics

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.

Seasonal Factors

In temperate areas, the peak incidence of measles infection occurs during late winter and spring.

Transmission

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.

Guidelines on Measles from the American Academy of Pediatrics

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.

Evidence of Immunity to Measles

Any of the following constitutes evidence of immunity to measles:

  • Documentation of age-appropriate vaccination with a live measles virus-containing vaccine (one dose for preschool-aged children, the second dose for children in kindergarten through 12th grade)
  • Laboratory evidence of immunity to measles
  • Laboratory confirmation of having had measles
  • Birth before 1957

Risk Factors

Risk factors for measles viral infection in all age groups include the following:

  • Underlying immunodeficiency caused by HIV or AIDS
  • Immunosuppression following receipt of an organ or a stem cell transplant
  • Leukemia, alkylating agents, or corticosteroid therapy, regardless of immunization status
  • Travel to areas where measles is endemic
  • Contact with travelers returning from areas where measles is endemic
  • Malnutrition
  • Pregnancy
  • Vitamin A deficiency
  • Loss of passive transferred maternal antibodies, usually between the first four to eight months, before the age of routine immunization

Clinical Presentation

Patient History

Healthcare providers should consider measles when evaluating individuals with a febrile rash. Ascertain the individuals:

  • vaccine status
  • recent travel history
  • contact with individuals who have a febrile rash
  • exposure to the measles virus

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.

Signs and Symptoms

Prodromal Phase (Early or Premonitory Symptoms of the Disease)

Measles typically begins with:

  • High fever (often greater than104o F or 40o C) that typically lasts 4 - 7 days.
  • Classic triad of (the “3 Cs”): (see images below)
    • Conjunctivitis
      • Ocular symptoms may also include:
      • Periorbital edema
      • Burning pain
      • Exudate in the conjunctival sac
    • Cough  
      • Runny nose
    • Coryza (runny nose)

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:

  • Malaise
  • Myalgias
  • Anorexia
  • Laryngeal involvement (less common):
    • Hoarseness
    • Aphonia

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.

Exanthem (Rash)

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

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

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

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:

  • Malnutrition
  • Immune deficiency disorders i.e. leukemia, HIV etc. which place children and adults at increased risk for severe infections and superinfections
  • Pregnancy
  • Vitamin A deficiency
  • Inadequate vaccination status

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

Common measles complications may include:

  • Otitis media - ear infections occur in one out of every 10 children and can result in permanent hearing loss
  • Bronchopneumonia - either direct viral pneumonia or secondary bacterial pneumonia
  • Laryngotracheobronchitis (i.e. croup)
  • Diarrhea - reported in less than one out of 10 individuals with measles

Severe

Severe complications may include:

  • Pneumonia - as many as one out of every 20 children with measles get pneumonia, the most common cause of death from measles in young children.
  • Encephalitis - about one child out of every 1,000 who gets measles will develop acute measles encephalitis which typically occurs two days to one week after the outbreak of the measles rash and begins with a very high fever, severe headache, convulsions and altered mentation.  Acute measles encephalitis can leave the child deaf and with permanent brain damage. It is fatal in about 10% of individuals.

Long-term

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

Rare complications of measles can range from mild to severe and may include:

  • Hemorrhagic measles
  • Purpura fulminans
  • Disseminated intravascular coagulation (DIC)
  • Exacerbation of tuberculosis
  • Transient loss of hypersensitivity reaction to tuberculin skin test
  • Hypocalcemia
  • Encephalomyelitis
  • Hyperesthesia and paresthesia
  • Keratitis which can lead to blindness (Measles remains a common cause of blindness in many developing countries).
  • Corneal ulceration (leading to corneal scarring)
  • Sinusitis
  • Lymphadenitis
  • Hilar lymphadenopathy
  • Pericarditis
  • Myocarditis
  • Interstitial pneumonitis
  • Pleural effusion
  • Stomatitis
  • Appendicitis
  • Hepatitis
  • Ileocolitis
  • Hepatosplenomegaly
  • Acute pancreatitis

Complications of Pregnancy

The complications of measles in the pregnant mother include:

  • Spontaneous abortion
  • Low birth weight baby
  • Premature birth of the fetus but perinatal transmission rates are low
  • Pneumonitis
  • Hepatitis
  • Subacute sclerosing panencephalitis (SSPE)

Diagnostic Work-up

Differential Diagnosis

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:

  • Dengue fever
  • Dermatologic manifestations of viral hemorrhagic fevers
  • Drug eruptions
  • Emergent treatment of acute conjunctivitis
  • Enteroviral infections
  • Erythema infectiosum (Fifth Disease)
  • Infectious mononucleosis
  • Kawasaki disease
  • Meningitis
  • Parvovirus B19 infection
  • Pediatric fever
  • Pediatric scarlet fever
  • Pediatric sepsis
  • Pediatrics, Roseola Infantum
  • Rocky mountain spotted fever
  • Rubella
  • Serum sickness
  • Syphilis
  • Systemic lupus erythematosus
  • Toxic shock syndrome

Laboratory Testing

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:

  • Serologic testing for measles-specific IgM or IgG titers (Antibody Assays)
  • Isolation of the Virus (Viral Cultures)
  • Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Evaluation

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.

Serologic testing

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.

Isolation of the Virus

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.

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.

Studies for Suspected Complications

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:

  • Increased protein
  • Normal glucose
  • Mild pleocytosis with a predominance of lymphocytes

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.

Treatment and Management

Supportive Care

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:

  • Maintenance of good hydration and replacement of fluids lost through diarrhea or emesis.
  • IV rehydration if dehydration is severe either through loss of fluids and electrolytes from emesis or diarrhea or from elevated fevers.
  • Fever management with standard antipyretics as appropriate.
  • Treatment of secondary infections (e.g. otitis media or bacterial pneumonia etc.) with appropriate antibiotics.
  • Consideration of vitamin A supplementation especially in children and individuals with clinical signs of vitamin A deficiency.
  • Consideration of post-exposure prophylaxis in unvaccinated contacts.
  • Timely tracing of contacts should be made a priority.

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.

Isolation

Airborne precautions are indicated for:

  • Hospitalized children during the period of communicability (i.e. 3 - 5 days before the appearance of a rash to 4 days after the rash develops in healthy children)
  • Hospitalized adults
  • The duration of illness in individuals who are immunocompromised.

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.

Medication

Medications used in the prevention or treatment of measles include measles virus vaccines, human immunoglobulin (IG), vitamin A and antivirals (e.g. ribavirin).

Vaccines

The following measles vaccines are available throughout the world:

The measles, mumps and rubella vaccine (M-M-R II) (MMR)

  • This live measles vaccine is usually given along with the attenuated rubella and mumps viruses to induce active immunity against the viruses that cause measles, mumps and rubella.
  • The MMR vaccine is most commonly used in the United States.
  • The MMR vaccine may provide some protection if administered within 72 hours of exposure to the measles virus.
  • The MMR vaccine does not alter the course of mumps or rubella following post-exposure to either the mumps or rubella viruses.

Live measles, mumps, rubella, and varicella virus vaccine (ProQuad) (MMRV)

  • This is a live vaccine that induces active immunity against viruses that cause measles, mumps, rubella, and varicella.

MMR Vaccine Recommendations

Children

  • The CDC recommends all children get two doses of MMR vaccine:
  • first dose of 0.5 ml SC at 12 through 15 months of age
  • second dose of 0.5 ml SC at 4 through 6 years of age
  • Children can receive the second dose earlier as long as it is at least 28 days after the first dose.
  • Students at Post-High School Educational Institutions
  • Students at post-high school educational institutions who do not have evidence of immunity against measles need two doses of MMR vaccine, separated by at least 28 days.

Adults

  • Adults born before 1957 are considered immune to measles and mumps.
  • All adults born in 1957 or later should have documentation of one or more doses of MMR vaccine unless contraindicated or laboratory evidence of immunity.
  • Adults who do not have evidence of immunity against measles should get at least one dose of MMR vaccine.
  • Ages 19 - 49: 0.5 mL SC; the second dose may be administered at least 28 days after the first dose.
  • Older than 50 years: administer 1 dose only.

All adults in the following risk categories should get a second dose of MMR vaccine:

  • Student in postsecondary education
  • Recent exposure
  • Occupational risk
  • Previously vaccinated with killed measles vaccine
  • Vaccinated with unknown type of measles vaccine during 1963 - 67

International Travelers

  • Before departure from the United States for international travel, individuals 6 months of age and older should be protected against measles.
  • Infants 6 through 11 months of age should receive one dose of MMR vaccine. Infants who get one dose of MMR vaccine before their first birthday should get two more doses (one dose at 12 through 15 months of age and another dose at least 28 days later).
  • Children 12 months of age and older should receive 2 doses of MMR before departure. The first dose should be administered on or after age 12 months and the second dose at least 4 weeks later.
  • Teenagers and adults born during or after 1957 who do not have evidence of immunity against measles should get two doses of MMR vaccine separated by at least 28 days prior to departure.

Catch-up Vaccination

  • All school-aged children and adolescents should have received 2 doses of 0.5 mL SC each.
  • Minimum time between 1st and 2nd dose of the MMR vaccine is 4 weeks.

Immunization in Pregnancy

  • Pregnant women who do not have evidence of immunity should receive the MMR vaccine upon delivery or termination of pregnancy and before discharge from the healthcare facility.
  • Pregnancy should be avoided for 28 days following MMR vaccine administration.
  • Perinatal HIV Infection
  • Revaccinate individuals who were vaccinated before the establishment of effective antiretroviral therapy (ART) with 2 appropriately spaced doses of MMR vaccine once effective ART has been established.

12 Months or Older with HIV Infection

  • Vaccinate all individuals with HIV infection who do not have evidence of current severe immunosuppression.

Post-exposure Prophylaxis with the MMR Vaccine

  • Prevention or modification of measles in exposed susceptible individuals may involve the administration of the MMR vaccine. The MMR vaccine is preventative if administered within 72 hours of exposure.
  • Infants 6 through 11 months should be given the MMR vaccine if administered within 72 hours of exposure.
  • Unvaccinated individuals who receive their first dose of the MMR vaccine within 72 hours after exposure may return to childcare, school or work except healthcare workers.

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.

Healthcare Personnel

Healthcare Personnel

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.

Post-exposure Prophylaxis:

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/Precautions

Contraindications to the MMR vaccine include:

  • Allergy to the antibiotic neomycin, gelatin or to any other component of the MMR vaccine.
  • Any individual who has ever had a life-threatening allergic reaction to a previous dose of the MMR vaccine.
  • Pregnant women should not get the MMR vaccine until after delivery because of the theoretical risk of vaccine virus transmission to the fetus.
  • Women should avoid getting pregnant for 4 weeks after vaccination with the MMR vaccine.
  • An individual in close contact with a pregnant female may receive the vaccine.
  • HIV/AIDS: CD4+ count less than 200 cells/mcL.
  • Severely immunocompromised individuals such as may occur in leukemia, lymphoma, generalized malignancy, congenital immunodeficiency.
  • Warning against giving live-virus measles vaccines to immunocompromised individuals with disorders associated with increased severity of viral infections (except individuals with HIV who do not have evidence of severe immunosuppression).
  • Receiving immunosuppressive therapy such as alkylating agents, antimetabolites, radiation or large doses of corticosteroids.
  • Postpone the MMR vaccination in individuals for at least a month after completion of a high-dose course of corticosteroids, such as prednisone.
  • Active, untreated tuberculosis.
  • Current febrile respiratory illness or febrile infection.
  • Individuals diagnosed with blood dyscrasias.
  • Individuals who have received antibodies (i.e., plasma, whole blood, any immune globulin) should have the MMR vaccine deferred for at least 5 months.

Precautions to the MMR vaccine include:

  • Syncope accompanied by transient visual disturbances reported with vaccines.
  • Postpone vaccination on individuals with moderate to severe acute illness (with or without fever).
  • Postpone vaccination on children who have severe diarrhea, moderate otitis media or moderate to severe vomiting with or without a fever.
  • Postpone vaccination on any individual who is experiencing a moderate or severe illness.
  • Use caution in individuals with a history of cerebral injuries, seizures, or conditions where stress to fever should be avoided.
  • Immune globulins may interfere with immune response if administered recently or concurrently.

Individuals may be vaccinated who are:

  • Experiencing a minor illness (e.g. upper respiratory infections with or without fever).
  • Breast-feeding (Vaccination of a woman who is breastfeeding poses no risk to the infant being breastfed).
  • Children who have experienced a severe egg allergy. (The ACIP recommends   routine vaccination of egg-allergic children without the use of special protocols or desensitization procedures).

MMRV Vaccine Recommendations

This is a live vaccine that induces active immunity against viruses that cause measles, mumps, rubella, and varicella (Chickenpox).

Children

  • Two doses of MMRV vaccine are recommended:
  • first dose of 0.5 ml SC at 12 through 15 months of age
  • second dose of 0.5 ml SC at 4 through 6 years of age but the second dose may be given up to 12 years of age if it is at least 3 months after the first dose.

Adults

  • Not recommended

Contraindications/Precautions

Contraindications to the MMRV vaccine include:

Children should not get the MMRV vaccine if they:

  • Have ever had a life-threatening allergic reaction to a previous dose of MMRV vaccine or to either MMR or varicella vaccine.
  • Have ever had a life-threatening reaction to gelatin or the antibiotic neomycin.
  • Have blood dyscrasia, leukemia, lymphoma, malignancy affecting bone marrow/lymphatic system or any other form of cancer.
  • Have HIV/AIDS, or another disease that renders the child immunodeficient.
  • Are being treated with drugs that affect the immune system, including high doses of oral steroids for 2 weeks or longer.
  • Are being treated for cancer with radiation or drugs.
  • Have active untreated TB.
  • Are pregnant
  • Have a fever >101.3°F (38.5°C)

Precautions to the MMRV vaccine include:

  • History of cerebral injury, individual/family history of seizures, any other condition where stress due to fever needs to be avoided.
  • Hypersensitivity to eggs.
  • Hypersensitivity to neomycin - may cause contact dermatitis.
  • Febrile seizures.

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.

MMR verses MMRV

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)?

  • Both options give the same protection.
  • There is one less shot with MMRV.
  • Children who got the first dose as MMRV have had more fevers and fever-related seizures (about 1 in 1,250) than children who got the first dose as separate shots of MMR and varicella vaccines on the same day (about 1 in 2,500).
  • Anyone 13 or older who needs protection from these diseases should get MMR and varicella vaccines as separate shots.
  • MMRV may be given at the same time as other vaccines.

Human Immunoglobulin (IG) Post-Exposure Prophylaxis

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.

  • Intramuscular IG (IGIM) should be given to all infants younger than 12 months of age who have been exposed to measles.
  • For infants’ age 6 through 11 months of age, the MMR vaccine can be given in place of IG, if administered within 72 hours of exposure.
  • Because pregnant women might be at higher risk for severe measles and its complications, intravenous IG (IGIV) should be administered to pregnant women without evidence of measles immunity who have been exposed to the measles.
  • People with severely compromised immune systems who are exposed to measles should receive IGIV regardless of immunologic or vaccination status because they might not be protected by the MMR vaccine.

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.

Human Immunoglobulin (IG) Recommendations

It is indicated for all contacts of individuals with measles who have no evidence of immunity against measles and who:

  • Reside in the same household
  • Are pregnant
  • Are immunocompromised
  • Are age 6 months to 1 year (morbidity is high in children younger than 1 year).
  • Are younger than 6 months who were born to mothers without measles immunity.
  • Are children and adolescents with HIV infection who were exposed to measles, regardless of their measles immunization status, unless they received IGIV (400 mg/kg as part of routine immunoprophylaxis) within 3 weeks of exposure to the measles virus.

Contraindications/Precautions

Contraindications to Human Immunoglobulin (IG) include:

  • Black Box Warnings
  • Thrombosis
  • Thrombosis may occur with immune globulin products.
  • Risk factors include advanced age, prolonged immobilization, hypercoagulable conditions, and history of thrombosis, estrogen use, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors.
  • For high risk individuals, the lowest possible dose and infusion rate should be administered, adequate hydration ensured before administration, blood viscosity assessed, and signs and symptoms of thrombosis continuously assessed.
  • Hypersensitivity to immune globulins or solution components
  • Selected IgA deficiency with known antibody against IgA
  • Severe thrombocytopenia or coagulation disorders
  • Hyperprolinemia (Hizentra contains the stabilizer L-proline)

Precautions to Human Immunoglobulin (IG) include:

  • Initial treatment should be done in a clinical setting due to the possibility of anaphylactic reactions.
  • May transiently impair efficacy of live attenuated viruses.
  • Passive transmission of antibodies may yield false positive serological tests (e.g. Coombs).
  • Products made from human plasma can contain infectious agents (e.g. viruses and, theoretically, Creutzfeldt-Jakob disease [CJD]).
  • Subcutaneous administration is associated with increased risk of hematoma.
  • Hemolytic anemia reported so monitor individuals CBC.
  • Renal dysfunction or renal failure has been associated with IG therapy so monitoring renal function and urine output are important.
  • Hyperproteinemia and hyponatremia may occur.
  • Aseptic meningitis syndrome has been reported.

Vitamin A Supplementation

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:

  • Infants younger than 6 months - 50,000 IU/day PO for 2 doses
  • Age 6 - 11 months - 100,000 IU/day PO for 2 doses
  • Older than 1 year - 200,000 IU/day PO for 2 doses
  • Children with clinical signs of vitamin A deficiency – the first 2 doses as appropriate for age, then a third age-specific dose given 2 - 4 weeks later

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 Recommendations

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/Precautions

Contraindications to Vitamin A supplementation include:

  • Hypersensitivity to vitamin A
  • IV use
  • Hypervitaminosis A
  • Malabsorption syndrome (Vitamin A is poorly absorbed orally.)
  • Pregnancy (dose > RDA)

Precautions to Vitamin A supplementation include:

  • Use caution if dosage is greater than 25,000 units/day.
  • Evaluate additional vitamin deficiencies if the diagnosis of vitamin A deficiency occurs (single vitamin A deficiency is rare).
  • Use with caution in renal impairment since Vitamin A toxicity has been reported.
  • Monitor prolonged administration over 25,000 units/day taking into account vitamin A intake from other dietary and supplement sources.

Antiviral Therapy

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.

Antiviral Therapy Recommendations

Ribavirin is not approved by the United States Food and Drug Administration (FDA) for any indication, and such use should be considered experimental.

Contraindications/Precautions

Contraindications to antiviral therapy include:

Black Box Warnings

Oral

  • Monotherapy is not effective for treatment of chronic hepatitis C virus (HCV) infection and should not be used alone for this indication.
  • Hemolytic anemia is the primary toxicity, which may result in worsening of cardiac disease and lead to fatal and nonfatal MI. Not to be used if history of significant or unstable cardiac disease.
  • Significant teratogenic and/or embryocidal effects demonstrated in all animal species exposed to ribavirin.
  • Half-life is 12 days, and drug may persist in nonplasma compartments for as long as 6 months.
  • Contraindicated during pregnancy and in the male partners of pregnant women.
  • Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both females and female partners of men taking ribavirin.
  • At least two reliable forms of effective contraception must be used during treatment and during the 6-month post treatment follow-up period.

Inhalation

  • Aerosolized ribavirin in individuals requiring mechanical ventilator assistance should be administered only by healthcare personnel and support staff familiar with this mode of administration and the specific ventilator being used.
  • Strictly follow procedures that minimize drug precipitate accumulation to avoid mechanical ventilator dysfunction.
  • Sudden respiratory function deterioration in infants may occur during initiation of aerosolized ribavirin.
  • Carefully monitor respiratory function during treatment.
  • If sudden deterioration of respiratory function occurs, stop treatment and reinstitute only with extreme caution, continuous monitoring, and possibly bronchodilator coadministration.
  • Aerosolized ribavirin is not indicated for adults.
  • Produces testicular lesions in rodents and is teratogenic in all animal species in which adequate studies have been conducted (rodents and rabbits).

Contraindications to antiviral therapy include:

  • General: hypersensitivity
  • Virazole: pregnancy; adults; nonsevere RSV infections
  • CrCl <50 mL/min
  • Pancreatitis
  • Hemoglobinopathies (e.g. thalassemia major, sickle cell anemia)
  • Coadministration with didanosine
  • Pregnancy or planning pregnancy, including men whose female partners are pregnant/planning to get pregnant
  • In combination with alpha interferons
  • Autoimmune hepatitis
  • Hepatic decompensation in individuals with cirrhosis

Precautions to antiviral therapy include:

  • Virazole: Mechanically ventilated patients
  • HCV
  • Preexisting cardiac disease
  • May need interruption if cardiovascular status deteriorates
  • Risk of hemolytic anemia
  • Do NOT use for influenza
  • Only Copegus studied in HCV/HIV coinfectees, however the modified dose is CDC recommended.
  • Use with caution with corresponding peginterferons.
  • Ribavirin may cause birth defects and/or death of the fetus
  • Avoid pregnancy
  • Risk of hemolytic anemia
  • Anemia associated with treatment may result in worsening of cardiac disease
  • Genotoxic and mutagenic: potential carcinogen
  • Ocular disorders reported when ribavirin is used in combination therapy with alpha interferons (e.g. decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages, cotton wool spots, optic neuritis, papilledema, serous retinal detachment)
  • Study in boys showed growth rate inhibited (i.e. height percentile decreases) with peginterferon alfa-2b plus ribavirin
  • Pancytopenia and bone marrow suppression reported when coadministered with pegylated interferon and azathioprine
  • Hepatic decompensation
  • Individuals with chronic hepatitis C (CHC) and cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS.
  • Cirrhotic CHC individuals coinfected with HIV receiving highly active antiretroviral therapy (HAART) and interferon alfa-2a with or without ribavirin appear to be at increased risk for the development of hepatic decompensation compared to individuals not receiving HAART

Reporting a Case of Measles

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:

  • Generalized rash lasting 3 days or longer
  • Temperature of 101.0°F (38.3°C) or higher
  • Cough, coryza, or conjunctivitis

Further, for reporting purposes for the CDC, cases are classified as follows:

  • Suspected - any febrile illness accompanied by rash.
  • Probable - a case that meets the clinical case definition, has noncontributory or no serologic or virologic testing, and is not epidemiologically linked to a confirmed case.
  • Confirmed - A case that is laboratory confirmed or that meets the clinical case definition and is epidemiologically linked to a confirmed case; a laboratory-confirmed case need not meet the clinical case definition.

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:

  • Communicating with public health officials from states with reported measles cases and providing technical assistance.
  • Gathering data reported by states on confirmed measles cases and evaluating and monitoring this data from a national perspective.
  • Testing specimens for difficult diagnostic cases of suspected measles infection when requested by states.
  • Using Advanced Molecular Detection (AMD) methods to determine measles virus genotypes and strains.
  • Providing rapid assistance on the ground during outbreak investigations, often through a formal request by the state health department.
  • Investing in state and local health departments for public health infrastructure and laboratory capacity to support front-line response to suspected and confirmed measles cases.
  • Alerting healthcare providers, healthcare facilities, and public health officials around the country about current outbreaks and providing vaccine policy and clinical guidance to healthcare providers.
  • Providing information to public and healthcare providers through a variety of media including the CDC website.

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.

Prognosis

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.

Conclusion

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?

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This course is applicable for the following professions:

Advanced Registered Nurse Practitioner (ARNP), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Registered Nurse (RN)

Topics:

Advance Practice Nurse Pharmacology Credit, Infection Control/Disease


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