This course will prepare healthcare professionals to participate in prevention and to identify and respond to a measles outbreak.
This course will prepare healthcare professionals to participate in prevention and to identify and respond to a measles outbreak.
After completing this course, the learner will be able to meet the following objectives:
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.
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.” 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 parent's 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.”
Measles, also known as morbilli, rubeola, or red measles, is a highly contagious infection caused by the measles virus. The measles virus is a single-stranded, negative-sense, enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae.
Molecular epidemiology of measles viruses is an important component in outbreak investigations and for global surveillance of circulating wild-type measles strains, i.e. measles viruses that are endemic to certain populations around the globe. During outbreaks, measles vaccine is administered to help control the outbreak, and in these situations, vaccine reactions may be mistakenly classified as measles cases. A small proportion of measles vaccine recipients experience rash and fever 10 – 14 days following vaccination. The vaccine strain of the 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.
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 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.
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 is 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 1850s, 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 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.1
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).2
Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.
In 1978, the CDC set a goal to eliminate measles from the United States by 1982. Although this goal was not met, the 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 the 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 designated geographic area, such as a region or country, for 12 months or longer in the presence of a well-performing surveillance system. This was possible due to a highly effective vaccination program and better measles control in the Americas region.
The continued circulation of measles in a community depends on the generation of susceptible hosts by the birth of children. In communities which generate insufficient new hosts, the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number of people capable of supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is about 250,000. In order 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.
Sustaining elimination requires maintaining high MMR vaccine coverage rates, particularly among preschool and school-aged children. 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 prevalent 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. An outbreak of measles is defined as a chain of transmission with three or more confirmed cases.
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.
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.1
From 1989 to 1991, a significant 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.
By 1997-1999, the incidence of measles had been reduced to a historic low (less than 0.5 cases per million individuals). In 2000, the transmission of endemic measles was declared eliminated in the United States.
In 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.
January 1 - July 31, 2008, remains the highest year-to-date since 1996. 131 cases of measles were reported to the CDC from 15 states. 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.
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. 2 out of every 3 individuals who developed measles were unvaccinated. A review by the CDC in 2014 concluded that "the elimination of endemic measles, rubella, and Congenital Rubella Syndrome (CRS) has been sustained in the United States.”
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. Almost half (22 or 49%) of these importations were travelers returning from the Philippines, where a large outbreak occurred beginning in October 2013. Fifteen outbreaks accounted for 227 (79%) of the 288 cases.
December 2014 to February 2015: The CDPH issued a press release and an Epidemic Information Exchange (Epi-X) notification regarding the California outbreak. This outbreak originated in late December 2014 in Disney theme parks in Orange County, California. As of February 11, 2015, a total of 125 measles cases with a rash which occurred had been confirmed in residents of the United States connected with the California outbreak.3
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 illustrates the continued importance of ensuring high measles vaccination coverage in the United States.
Because measles remains endemic in countries in five out of the six WHO regions of the world, this underscores the importance of ensuring age-appropriate vaccination for all individuals before international travel to any region of the world.
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.
Individuals with measles often seek medical care. Early recognition of suspected measles cases and the 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:
In order 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.1
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:
The Advisory Committee on Immunization Practices (ACIP) routine immunization schedule is essential to limit measles importations and the spread of the disease. So as 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, of the increased risk of exposure 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 the 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.
Even though a safe and cost-effective vaccine is available, in 2017, there were 110,000 measles deaths globally, mostly among children under the age of five.4 In developing countries, measles causes 15,000 - 60,000 cases of blindness per year.
Measles vaccination resulted in an 80% drop in measles deaths between 2000 and 2017 worldwide. In 2017, about 85% of the world's children received one dose of measles vaccine by their first birthday through routine health services, up from 72% in 2000. During 2000-2017, measles vaccination prevented an estimated 21.1 million deaths making measles vaccine one of the best buys in public health.4
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.
The following are the reported measles cases in regions of the world, over time.5
Region of the Americas
Eastern Mediterranean Region
South-East Asia Region
Western Pacific Region
Measles, historically, has been thought to be a disease of childhood. Measles infection, though, can occur in unvaccinated or partially vaccinated individuals of any age or in those with compromised immunity.
Unvaccinated young children are at the highest risk. Age-specific attack rates may be highest in susceptible infants younger than 12 months, school-aged children, or young adults, depending on local immunization practices and incidence of the disease.
In densely populated, underdeveloped countries, measles is most common in children younger than 2 years.
Unvaccinated males and females are equally susceptible to infection by the measles virus. Following acute measles, increased mortality has been observed among females of all ages, but it is most marked in adolescents and young adults. Excessive non-measles related mortality has also been observed among female recipients of high-titer measles vaccines in Senegal, Guinea Bissau, and Haiti.
Measles affects people of all races.
In temperate areas, the peak incidence of measles infection occurs during late winter and spring.
The measles virus is a highly contagious airborne virus which lives in the nose and throat mucus of an infected individual. Measles spreads when an infected individual breathes, coughs or sneezes. The measles virus can also live for up to two hours in an airspace where the infected individual breathed, coughed or sneezed. If other individuals breathe the contaminated air or touch an infected surface, then touch their eyes, nose, or mouth, they can become infected. Thus, the virus can be transmitted by direct contact with infectious droplets on surfaces and in the air for up to two hours after an infected individual leaves an area.
Nine out of ten individuals (90%) who share living space with an infected individual and are not immune will catch the measles. Infected individuals are infectious to others from four days before to four days after the start of the rash. Individuals usually only get measles once.
Measles is a disease of humans. The measles virus is not spread by any other animal species.
Any of the following constitutes evidence of immunity to measles:
Risk factors for measles viral infection in all age groups include the following:
Healthcare providers should consider measles when evaluating individuals with a febrile rash. Ascertain the individuals:
The incubation period from exposure to onset of measles symptoms ranges from 7 to 14 days (average, 10 - 12 days). Individuals are contagious from 1 - 2 days before the onset of symptoms. Healthy children are considered to be contagious from 4 days before to 4 days after the rash appears. Immunocompromised individuals can be contagious during the duration of the illness.
Prodromal Phase (Early or Premonitory Symptoms of the Disease) typically begins with:
Catarrhal inflammation of the respiratory tract occurs concomitantly with the ocular symptoms or soon thereafter resulting in the coughing, sneezing and coryza.
Other symptoms may include:
Enanthem (Mucous Membrane Eruption), generally appears 2 - 4 days after the onset of the prodromal phase and lasts 3 - 5 days. Koplik spots - 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 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) often appears 1 - 2 days after the appearance of Koplik spots. Blanching, erythematous macules and papules typically start behind the ears or on the face or neck at the hairline. Mild pruritus may also occur.
Immunocompromised individuals may not develop a rash. The rash may be absent in individuals with underlying deficiencies in cellular immunity.
Within 48 hours, the lesions coalesce into patches and plaques that spread cephalocaudally to the trunk and extremities, including the palms and soles. It begins 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.
The entire course of uncomplicated measles, from late prodrome to resolution of fever and rash, is 7 - 10 days. The cough may be the final symptom to disappear.
Modified measles is a milder form of measles that occurs in individuals who have received serum immunoglobulin after their exposure to the measles virus. Similar but milder signs and symptoms may still occur. The incubation period may be as long as 21 days.
Atypical measles occurs in individuals who were vaccinated with the original killed-virus measles vaccine between 1963 and 1967. These individuals failed to elicit long-lived protective antibody and a cytotoxic T-lymphocyte response to the measles virus. These individuals have developed incomplete immunity to the measles virus. The live-attenuated vaccine replaced the killed-virus measles vaccine in 1967 and is not associated with atypical measles.
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.
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 such as otitis media, bronchopneumonia, laryngotracheobronchitis (i.e., croup), and diarrhea are more common in young children.
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 with6:
As many as 1 out of every 20 children with measles gets pneumonia, the most common cause of death from measles in young children.
About 1 child out of every 1,000 who get measles will develop encephalitis (swelling of the brain) that can lead to convulsions and can leave the child deaf or with intellectual disability.
Nearly 1 to 3 of every 1,000 children who become infected with measles will die from respiratory and neurologic complications.
Measles may cause pregnant women who have not had the MMR vaccine to give birth prematurely or have a low-birth-weight baby.
All individuals with complications, no matter what age, may need to be hospitalized and could face death.
Common measles complications may include:
Severe complications may include:
Rare complications of measles can range from mild to severe and may include:
The complications of measles in the pregnant mother include:
Subacute sclerosing panencephalitis (SSPE), a very rare, fatal complication of measles, is a degenerative CNS disease that can result from a persistent measles infection which was acquired earlier in life. SSPE generally develops 7 to 10 years (the mean incubation period for SSPE is approximately 10.8 years) after an individual has measles, even though the individual seems to have fully recovered from the illness. Among individuals who contracted measles during the resurgence in the United States from 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.
The diagnosis of measles is usually determined from the classic clinical picture, including the classic triad of cough, coryza, and conjunctivitis, pathognomonic Koplik spots and the characteristic cephalocaudal progression of the morbilliform exanthem.
Other diagnoses to be considered include the following:
Although the diagnosis of measles is usually determined from the classic clinical picture, laboratory identification and confirmation of the diagnosis are necessary for public health and outbreak control.
Laboratory confirmation is achieved by means of the following:
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 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 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 three weeks from the onset of the illness, a delay too long to permit implementation of effective outbreak control measures.
In atypical measles, laboratory evaluation of serum/blood reveals very low titers of measles antibody early in the course of the disease, followed by extremely high measles IgG antibody titers (e.g., 1:1,000,000).
IgG levels can be explained by current infection, immunity due to past infection or vaccination, or maternal antibodies present in infants younger than 15 months.
Blood for serologic testing can be collected by venipuncture or by finger/heel stick in tubes without additives - either a plain, red-top tube or a serum separator tube. The preferred volume for IgM and/or IgG testing at the CDC is 0.5 – 1.0 ml of serum but testing can be done with as little as 0.1 ml if necessary.
Throat swabs and nasal swabs can be sent on viral transport medium or a viral culturette swab to isolate the measles virus.
Urine specimens can be sent in a sterile container for viral culture.
Viral genotyping in a reference laboratory may determine whether an isolate is endemic or imported.
In immunocompromised individuals, who may have poor antibody responses that preclude serologic confirmation of measles, isolation of the virus from infected tissue or identification of measles antigen by means of immunofluorescence may be the only feasible method of confirming the diagnosis.
RT-PCR evaluation is highly sensitive at visualizing measles virus RNA and can rapidly confirm the diagnosis in blood, throat, nasopharyngeal, or urine specimens. The samples should be collected upon the first contact with a suspected case of measles when the serum sample for diagnosis is drawn.
A complete blood cell count (CBC) may reveal leukopenia with a relative lymphocytosis and thrombocytopenia. Liver function test (LFT) results may show elevated transaminase levels in individuals with measles hepatitis.
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.
If encephalitis is suspected, a lumbar puncture should be performed. CSF examination may reveal:
Tissue Analysis and Histologic Findings: A skin biopsy from a lesion of the morbilliform eruption may show spongiosis and vesiculation in the epidermis with scattered dyskeratotic keratinocytes. Occasional lymphoid multinucleated giant cells (≤ 100 nm in diameter) can be identified in biopsies of Koplik spots, in dermal or epithelial rashes, in hair follicles and acrosyringium and in lung or lymphoid tissue. These findings are not specific, but they are suggestive of a viral exanthem. Brain biopsies of individuals with measles encephalitis can reveal demyelination, vascular cuffing, gliosis, and infiltration of fat-laden macrophages near blood vessel walls.
There is no specific antiviral therapy for measles. Medical care is primarily supportive in nature and focused on relieving symptoms and treating complications such as bacterial infections. Supportive care in the treatment of measles is as follows:
Hospitalization may be indicated for the treatment of measles complications (e.g., bacterial superinfection, pneumonia, dehydration, croup, etc.). Individuals with severe complicating infections (e.g., encephalomyelitis) should be admitted for observation and antibiotics given, as appropriate, to their clinical condition.
Individuals should receive regular follow-up care with a primary care physician for surveillance of complications which may arise from the measles infection.
Airborne precautions are indicated for:
In healthcare settings, healthcare providers should follow respiratory etiquette and airborne precautions. Regardless of presumptive immunity status, all healthcare staff entering the room should use respiratory protection consistent with airborne infection control precautions (use of an N95 respirator or a respirator with similar effectiveness in preventing airborne transmission). Because of the possibility, albeit low, of MMR vaccine failure in healthcare staff exposed to infected individuals, they should all observe airborne precautions in caring for individuals with measles. The preferred placement for individuals who require airborne precautions is in a single-patient airborne infection isolation room (AIIR).
Healthcare providers without evidence of immunity who have been exempted from measles vaccination for medical, religious, or other reasons and who do not receive appropriate PEP within the appropriate timeframe should be excluded from affected institutions in the outbreak area until 21 days after the onset of rash in the last case of measles.
Medications used in the prevention or treatment of measles include measles virus vaccines, human immunoglobulin (IG), vitamin A and antivirals (e.g., ribavirin).
The measles, mumps and rubella vaccine (M-M-R II) (MMR) are available worldwide. 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 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.
MMR Vaccine Recommendations:
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.
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.
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.
Contraindications to the MMR vaccine include:
Precautions to the MMR vaccine include:
Individuals may be vaccinated who are:
This is a live vaccine that induces active immunity against viruses that cause measles, mumps, rubella, and varicella (Chickenpox).
Contraindications to the MMRV vaccine include:
Precautions to the MMRV vaccine include:
Early findings from an ongoing CDC study show that children who get an MMRV vaccine may be twice more likely to have a febrile seizure 7 - 10 days after getting the vaccine than children who get MMR and varicella vaccines (by 2 separate injections) at the same healthcare visit.
Children may also get these vaccines as two separate shots: MMR (measles, mumps, rubella) and varicella vaccines. The essential question remains: 1 Shot (MMRV) or 2 Shots (MMR and Varicella)?
Human Immunoglobulin (IG) prevents or modifies the measles virus in susceptible contacts if administered within 6 days of exposure.2 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, bacterial, parasitic, and mycoplasma antigens. These pooled human immune globulins also provide passive immunity through an increase in antibody titer and antigen-antibody reaction potential.
Post-exposure prophylaxis with human immunoglobulin (IG) should be administered to individuals who are at risk for severe illness and complications from measles, such as infants younger than 12 months of age, pregnant women without evidence of measles immunity, and individuals with severely compromised immune systems.
IG should not be used to control measles outbreaks, but rather to reduce the risk for infection and complications in the individuals receiving it. IGIM can be given to other individuals who do not have evidence of immunity against measles, but priority should be given to individuals exposed in settings with intense, prolonged, close contact, such as 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.
IG is indicated for all contacts of individuals with measles who have no evidence of immunity against measles and who:
Contraindications to Human Immunoglobulin (IG) include:
Precautions to Human Immunoglobulin (IG) include:
Vitamin A supplementation has been associated with an approximately 50% reduction in morbidity and mortality and appears to help prevent eye damage and blindness.
Because Vitamin A deficiency is associated with severe disease from measles, the WHO recommends all children diagnosed with measles should receive vitamin A supplementation regardless of their country of residence, based on their age, as follows:
Vitamin A supplementation plays a role in embryonic development, visual adaptation to darkness, immune function, and maintenance of epithelial cells. Vitamin A is a fat-soluble vitamin needed for the growth of skin, bones, and male and female reproductive organs. Vitamin A can be found in liver, butter, eggs, green leafy vegetables, colorful fruits and vegetables such as carrots, mango, pumpkin and sweet potatoes.
Vitamin A supplementation varies by age, dosage recommendations, route of administration, potential drug interactions, potential adverse effects, contraindications and cautions, pregnancy and lactation status.
Vitamin A supplementation can be found under such names as: Retinol, Aquasol A, Vitamin A, retinyl acetate, retinyl palmitate, A-25, Gordons-Vite A.
Vitamin A supplementation is indicated for all individuals with measles who are:
Contraindications to Vitamin A supplementation include:
Precautions to Vitamin A supplementation include:
Ribavirin, a guanosine analogue, is for experimental use only. Its mechanism of action is not fully defined, but it may inhibit the initiation and elongation of RNA fragments by inhibiting polymerase activity, which in turn results in the inhibition of viral protein synthesis.
The measles virus is susceptible to ribavirin in vitro. Although ribavirin (either IV or aerosolized) has been used to treat severely affected and immunocompromised individuals with acute measles or subacute sclerosing panencephalitis (SSPE), no controlled trials have been conducted.
Ribavirin dosage varies by age, route of administration, potential drug interactions, possible adverse effects, cautions and contraindications, pregnancy and lactation precautions and toxicity.
Antiviral therapy can be found under such brand names as Ribavirin, Moderiba, Virazole, Rebetol, Ribasphere, RibaPak, and Copegus.
Ribavirin is not approved by the United States Food and Drug Administration (FDA) for any indication, and such use should be considered experimental.
Contraindications to antiviral therapy include:
Contraindications to antiviral therapy include:
Because the transmission of wild-type measles has been interrupted in the United States and all recent epidemics in the United States have been linked to imported cases, immediately reporting any suspected case of measles to a local or state health department is imperative. Obtaining serum for IgM antibody testing as soon as possible (i.e., on or after the third day of rash) is a priority.
The Centers for Disease Control and Prevention (CDC) clinical case definition for reporting purposes requires only the following:
Further, for reporting purposes for the CDC, cases are classified as follows:
State and local health departments have the lead in investigating measles cases and outbreaks when they occur. The CDC helps and supports health departments in these investigations by:
In order to maintain reference stocks of viruses and provide facilities capable of conducting viral sequencing, two global Measles Strain Banks have been established.
The Measles, Mumps, Rubella and Herpesvirus Laboratory Branch of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA, and Health Protection Agency (HPA) in London, UK, were selected to serve this purpose. The Health Protection Agency in London, UK, contains sequence information from more than 10,000 measles samples.
The Measles Nucleotide Surveillance (MeaNS) initiative was developed as a web-accessible and quality-controlled nucleotide database for the WHO Measles Laboratory Network. This database is used as a tool to track measles sequence diversity and monitor the elimination of virus strains. Full access to MeaNS is given only to members of the WHO Measles and Rubella Laboratory Network (LabNet). Upon request, viral sequencing and analysis can be provided for measles virus characterization as well as storage of viral strains. Sequences submitted to MeaNS are automatically submitted to the WHO Global Measles Genotype Database at the WHO Headquarters in Geneva. Sequences can also be submitted to GenBank. Measles sequences in GenBank are imported into MeaNS on a bi-weekly basis.
The prognosis for measles is generally good with the majority of individuals surviving the infection. The measles infection only occasionally is fatal. The CDC reports that the childhood mortality rate from measles infection in the United States is 0.1 - 0.2%. However, many complications and sequelae may develop. Measles remains a major cause of childhood blindness in developing countries.
Globally, measles remains one of the leading causes of death in young children.
Case-fatality rates are higher among children younger than 5 years of age. The highest fatality rates are among infants 4 - 12 months of age and in children who are immunocompromised because of human immunodeficiency virus (HIV) infection or other causes.
Complications of measles are more likely to occur in individuals younger than 5 years or older than 20 years of age. Morbidity and mortality are increased in individuals with immune deficiency disorders, malnutrition, vitamin A deficiency, and inadequate vaccination.
Thus, prevention remains a global priority. Early diagnosis and treatment affects the outcome in all age groups and reduces the morbidity and mortality from the complications of measles.
Unsubstantiated claims that suggest an association between the measles vaccine and autism have resulted in reduced vaccine use and contributed to a recent resurgence of measles in countries where immunization rates have fallen to below the level needed to maintain herd immunity.
Considering that for industrialized countries such as the United States, endemic transmission of measles may be reestablished if measles immunity falls to less than 93 - 95%, efforts to ensure high immunization rates among individuals in both developed and developing countries must be sustained.
So the essential question remains, Are you willing to risk your health or the health of your loved ones including children for philosophical, legal, religious or personal beliefs, as well as, indirectly the health and well-being of your entire community by not choosing to prevent a disease which is so easily preventable?