Most viruses that infect humans can affect both adults and children and are discussed elsewhere in THE MANUAL. Viruses with specific effects on neonates are discussed in Infections in Neonates Overview of Neonatal Infections Neonatal infection can be acquired In utero transplacentally or through ruptured membranes In the birth canal during delivery (intrapartum) From external sources after birth (postpartum) Common... read more . This topic covers a viral infection that is typically acquired during childhood (although it may also affect unvaccinated adults).
Worldwide, measles infected about 10 million people and causes about 100,000 to 200,000 deaths each year, primarily in children ( 1 General reference Measles is a highly contagious viral infection that is most common among children. It is characterized by fever, cough, coryza, conjunctivitis, an enanthem (Koplik spots) on the oral mucosa... read more ). These numbers can vary dramatically over a short period of time depending on the vaccination status of the population. Measles is uncommon in the US because of routine childhood vaccination, and endemic measles was declared eliminated in the US in 2000. An average of 63 cases/year were reported to the Centers for Disease Control and Prevention (CDC) from 2000 to 2007. However, in 2019, incidence in the US had risen to a peak of 1282 cases, the highest number reported since 1992. The increase has primarily been due to imported cases with subsequent spread among unvaccinated groups (see the CDC's Measles Cases and Outbreaks  page). Parental refusal of vaccination is an increasing cause of the increase in vaccine-preventable diseases in children. In 2020, only 13 cases were reported in the US amid the COVID-19 global pandemic.
Pathophysiology of Measles
Measles is caused by a paramyxovirus and is a human disease with no known animal reservoir or asymptomatic carrier state. It is extremely communicable; the secondary attack rate is > 90% among susceptible people who are exposed.
Measles is spread mainly by secretions from the nose, throat, and mouth during the prodromal or early eruptive stage. Communicability begins several days before and continues until several days after the rash appears. Measles is not communicable once the rash begins to desquamate.
Transmission is typically by large respiratory droplets that are discharged by cough and briefly remain airborne for a short distance. Transmission may also occur by small aerosolized droplets that can remain airborne (and thus can be inhaled) for up to 2 hours in closed areas (eg, in an office examination room). Transmission by fomites seems less likely than airborne transmission because the measles virus is thought to survive only for a short time on dry surfaces.
An infant whose mother has immunity to measles (eg, because of previous illness or vaccination) receives antibodies transplacentally; these antibodies are protective for most of the first 6 to 12 months of life. Lifelong immunity is conferred by infection. In the US, almost all measles cases are imported by travelers or immigrants, with subsequent indigenous transmission occurring primarily among unvaccinated people.
Symptoms and Signs of Measles
After a 7- to 14-day incubation period, measles begins with a prodrome of fever, coryza, hacking cough, and tarsal conjunctivitis. Pathognomonic Koplik spots appear during the prodrome, before the onset of rash, usually on the oral mucosa opposite the 1st and 2nd upper molars. The spots resemble grains of white sand surrounded by red areolae. They may be extensive, producing diffuse mottled erythema of the oral mucosa. Sore throat develops.
The rash appears 3 to 5 days after symptom onset, usually 1 to 2 days after Koplik spots appear. It begins on the face in front of and below the ears and on the side of the neck as irregular macules, soon mixed with papules. Within 24 to 48 hours, lesions spread to the trunk and extremities (including the palms and soles) as they begin to fade on the face. Petechiae or ecchymoses may occur with severe rashes.
During peak disease severity, a patient’s temperature may exceed 40° C, with periorbital edema, conjunctivitis, photophobia, a hacking cough, extensive rash, prostration, and mild itching. Constitutional symptoms and signs parallel the severity of the eruption and the epidemic. In 3 to 5 days, the fever falls, the patient feels more comfortable, and the rash fades rapidly, leaving a coppery brown discoloration followed by desquamation.
Immunocompromised patients may not have a rash and can develop severe, progressive giant cell pneumonia.
Complications of measles include
Acute thrombocytopenic purpura
Subacute sclerosing panencephalitis
Pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more due to measles virus infection of the lungs occurs in about 5% of patients, even during apparently uncomplicated infection; in infants, it is a common cause of death.
Bacterial superinfections include pneumonia, laryngotracheobronchitis, and otitis media. Measles transiently suppresses delayed hypersensitivity, which can worsen active tuberculosis and temporarily prevent reaction to tuberculin and histoplasmin antigens in skin tests. Bacterial superinfection is suggested by pertinent focal signs or a relapse of fever, leukocytosis, or prostration.
Acute thrombocytopenic purpura may occur after infection resolves and cause a mild, self-limited bleeding tendency; occasionally, bleeding is severe.
Encephalitis Encephalitis Encephalitis is inflammation of the parenchyma of the brain, resulting from direct viral invasion or occurring as a postinfectious immunologic complication caused by a hypersensitivity reaction... read more occurs in 1/1000 to 2000 cases, usually 2 days to 2 weeks after onset of the rash, often beginning with recrudescence of high fever, headache, seizures, and coma. Cerebrospinal fluid usually has a lymphocyte count of 50 to 500/mcL and a mildly elevated protein level but may be normal initially. Encephalitis may resolve in about 1 week or may persist longer, causing morbidity or death.
Transient hepatitis and diarrhea may occur during an acute infection.
Subacute sclerosing panencephalitis Subacute Sclerosing Panencephalitis (SSPE) Subacute sclerosing panencephalitis is a progressive, usually fatal brain disorder occurring months to usually years after an attack of measles. It causes mental deterioration, myoclonic jerks... read more (SSPE) is a rare, progressive, ultimately fatal, late complication of measles.
Atypical measles syndrome is a complication that occurred in people vaccinated with the original killed-virus measles vaccines, which have not been used since 1968. These older vaccines altered disease expression in some patients who were incompletely protected and subsequently infected with wild-type measles. Measles manifestations developed more suddenly and significant pulmonary involvement was more common. Atypical measles is of note mainly because patients (now in their 50s and beyond) born while this vaccine was in use may report a history of both measles vaccination and measles.
Diagnosis of Measles
Viral detection via culture or reverse transcription–polymerase chain reaction (RT-PCR)
Typical measles may be suspected in an exposed patient who has coryza, conjunctivitis, photophobia, and cough but is usually suspected only after the rash appears. Diagnosis is usually clinical, by identifying Koplik spots or the rash in an appropriate clinical context. A complete blood count is unnecessary but, if obtained, may show leukopenia with a relative lymphocytosis.
Laboratory confirmation is necessary for public health and outbreak control purposes. It is most easily done by demonstration of the presence of measles IgM antibody in an acute serum specimen or by viral culture or RT-PCR of throat swabs, blood, nasopharyngeal swabs, or urine samples. A rise in IgG antibody levels between acute and convalescent sera is highly accurate, but obtaining this information delays diagnosis. All cases of suspected measles should be reported to the local health department even before laboratory confirmation.
Differential diagnosis includes rubella Rubella ( See also Congenital Rubella.) Rubella is a contagious viral infection that may cause adenopathy, rash, and sometimes constitutional symptoms, which are usually mild and brief. Infection during... read more , scarlet fever Scarlet fever Streptococci are gram-positive aerobic organisms that cause many disorders, including pharyngitis, pneumonia, wound and skin infections, sepsis, and endocarditis. Symptoms vary with the organ... read more , drug rashes Drug Eruptions and Reactions Drugs can cause multiple skin eruptions and reactions. The most serious of these are discussed elsewhere in THE MANUAL and include Stevens-Johnson syndrome and toxic epidermal necrolysis, hypersensitivity... read more (eg, resulting from phenobarbital or sulfonamides), serum sickness ( see Table: Some Causes of Urticaria Some Causes of Urticaria ), roseola infantum Roseola Infantum Roseola infantum is an infection of infants or very young children caused by human herpesvirus 6B (HHV-6B) or, less commonly, HHV-7. The infection causes high fever and a rubelliform eruption... read more , infectious mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more , erythema infectiosum Erythema Infectiosum Erythema infectiosum, acute infection with parvovirus B19, causes mild constitutional symptoms and a blotchy or maculopapular rash beginning on the cheeks and spreading primarily to exposed... read more , and echovirus and coxsackievirus infections ( see Table: Some Respiratory Viruses Some Respiratory Viruses ). Manifestations can also resemble Kawasaki disease Kawasaki Disease Kawasaki disease is a vasculitis, sometimes involving the coronary arteries, that tends to occur in infants and children between the ages of 1 year and 8 years. It is characterized by prolonged... read more and cause diagnostic confusion in areas where measles is very rare.
Some of these conditions can be distinguished from typical measles as follows:
Rubella: A recognizable prodrome is absent, fever and other constitutional symptoms are absent or less severe, postauricular and suboccipital lymph nodes are enlarged (and usually tender), and duration is short.
Drug rashes: A drug rash often resembles the measles rash, but a prodrome is absent, there is no cephalocaudal progression or cough, and there is usually a history of recent drug exposure.
Roseola infantum: The rash resembles that of measles, but it seldom occurs in children > 3 years of age. Initial temperature is usually high, Koplik spots and malaise are absent, and defervescence and rash occur simultaneously.
Prognosis for Measles
Mortality is about 2/1000 in the US but is much higher in medically underserved areas. Undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more and vitamin A deficiency Vitamin A Deficiency Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects (eg... read more may predispose to mortality. The CDC estimates that worldwide about 100,000 to 200,000 people die each year of measles, typically from pneumonia or encephalitis.
Treatment of Measles
For children, vitamin A
Treatment of measles is supportive, including for encephalitis.
Hospitalized patients with measles should be managed with standard and airborne precautions. Single-patient airborne infection isolation rooms and N-95 respirators or similar personal protective equipment are recommended. Otherwise healthy outpatients with measles are most contagious for 4 days after the development of the rash and should severely limit contact with others during their illness.
Vitamin A supplementation has been shown to reduce morbidity and mortality due to measles in children in medically underserved areas. Because low serum levels of vitamin A are associated with severe disease due to measles, vitamin A treatment is recommended for all children with measles. The dose is given orally once a day for 2 days and depends on the child’s age:
> 1 year: 200,000 international units (IU)
6 to 11 months: 100,000 IU
< 6 months: 50,000 IU
In children with clinical signs of vitamin A deficiency Vitamin A Deficiency Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects (eg... read more , an additional single, age-specific dose of vitamin A is repeated 2 to 4 weeks later.
Prevention of Measles
A live-attenuated virus vaccine Measles, Mumps, and Rubella (MMR) Vaccine The measles, mumps, and rubella (MMR) vaccine effectively protects against all 3 infections. People who are given the MMR vaccine according to the US vaccination schedule are considered protected... read more containing measles, mumps, and rubella is routinely given to children in most nations that have a robust health care system (also see Table: Recommended Immunization Schedule for Ages 0–6 Years Recommended Immunization Schedule for Ages 0–6 Years and see Table: Recommended Immunization Schedule for Ages 7–18 Years Recommended Immunization Schedule for Ages 7–18 Years ). Two doses are recommended:
The first dose is recommended at age 12 to 15 months but can be given as young as age 6 months during a measles outbreak or before international travel.
The second is given at age 4 to 6 years.
Infants immunized at < 1 year of age still require 2 additional doses given after the first birthday. Vaccine provides long-lasting immunity and has decreased measles incidence in the US by 99%. The vaccine causes mild or inapparent, noncommunicable infection. Fever > 38° C occurs 5 to 12 days after inoculation in 5 to 15% of vaccinees and can be followed by a rash. Central nervous system reactions are exceedingly rare; the measles vaccine does not cause autism Measles-mumps-rubella (MMR) vaccine Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the use and schedule of vaccines in children. These concerns have led some parents... read more .
Contraindications to the vaccine include generalized cancers (eg, leukemia, lymphoma), immunodeficiency, and therapy with immunosuppressants (eg, corticosteroids, irradiation, alkylating agents, antimetabolites). HIV infection is a contraindication only if immunosuppression is severe (CDC immunologic category 3 with CD4 < 15%); if not, the risks of wild measles outweigh the risk of acquiring measles from the live vaccine. Reasons to defer vaccination include pregnancy, serious febrile illness, active untreated tuberculosis, or recent administration of antibody (as whole blood, plasma, or any immune globulin). Duration of deferral depends on the type and dose of immune globulin preparation given but may be as long as 11 months.
Prevention in susceptible contacts is possible by giving the vaccine within 3 days of exposure. If vaccine should be deferred, immune globulin 0.50 mL/kg IM (maximum dose, 15 mL) is given immediately (within 6 days), with vaccination given 5 to 6 months later if medically appropriate. Exposed, severely immunodeficient patients, regardless of vaccination status, and pregnant women who are not immune to measles are given immune globulin 400 mg/kg IV. Immune globulin should not be given simultaneously with vaccine.
In an institutional outbreak (eg, schools), susceptible contacts who refuse or cannot receive vaccination and who also do not receive immune globulin should be excluded from the affected institution until 21 days after onset of rash in the last case. Exposed, susceptible health care workers should be excluded from duty from 5 days after their first exposure to 21 days after their last exposure, even if they receive postexposure prophylaxis.
Incidence of measles is highly variable depending on the vaccination rate in the population.
Measles is highly transmissible, developing in > 90% of susceptible contacts.
Measles causes about 100,000 to 200,000 deaths annually, primarily in children in medically underserved areas; pneumonia is a common cause, whereas encephalitis is less common.
Treatment is mainly supportive, but children should also receive vitamin A supplementation.
Universal childhood vaccination is imperative unless contraindicated (eg, by active cancer, use of immunosuppressants, or HIV infection with severe immunosuppression).
Give postexposure prophylaxis to susceptible contacts within 3 days of exposure; use vaccine unless contraindicated, in which case give immune globulin.
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
CDC: Measles Cases and Outbreaks statistics
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