By Dheeraj Kumar, MD and Camille Sabella, MD
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Despite widespread vaccination against measles in the United States, outbreaks continue to occur. Clinicians should be able to recognize its distinctive clinical picture so that isolation measures can be instituted promptly, susceptible contacts immunized, and public health agencies notified. Vaccination is safe for most people and should be strongly promoted for all healthy children.
Measles continues to rear its head in the United States. Because it is so contagious, even the few cases introduced by travelers quickly spread to susceptible contacts. Life-threatening and severely disabling complications can occur, although this is rare. Widespread immunization and prompt recognition and isolation of contacts are key to controlling outbreaks. This article reviews the epidemiology of measles, describes its distinctive clinical picture, and provides recommendations for infection control and prevention, including in immunosuppressed populations.
Measles is serious and highly contagious
Up to 90% of susceptible people develop measles after exposure, making it one of the most contagious of infections. The virus is transmitted by airborne spread when an infected person coughs or sneezes, or by direct contact with infectious droplets. The virus can remain infectious in the air or on a surface for up to two hours.1 Worldwide, an estimated 20 million people are infected with measles each year, and 146,000 die of complications. In 1980, before widespread vaccination, 2.6 million deaths were attributable to measles annually. In the United States before the introduction of measles vaccine in 1963, measles was a significant cause of disease and death: an estimated 3 to 4 million people were infected annually, although only about 549,000 were reported. There were 48,000 hospitalizations, 1,000 cases of permanent brain damage from measles encephalitis, and 495 deaths annually.2
Outbreaks still occur regularly
In 2000, measles was declared eliminated from the United States,3 but annual outbreaks have occurred since then as a result of cases imported from other countries and their subsequent transmission to unvaccinated people. From 2001 to 2012, a median of four outbreaks and 60 cases were reported annually to the US Centers for Disease Control and Prevention.4 In January 2015, a multistate measles outbreak originating in Disneyland in California was recognized. As of April 17, when the outbreak was declared over, 111 measles cases from seven states had been linked to this outbreak.5 Of the evaluable cases, 44% were in unvaccinated people and 38% were in those whose vaccination status was unknown or undocumented. The median age of patients was 21, and 20% required hospitalization. This outbreak, as well as four other smaller US outbreaks the same year, underscores the transmissibility of the virus in populations containing only a small percentage of unvaccinated people.6
Distinctive clinical picture
The incubation period for measles infection is 7 to 21 days, with most cases becoming apparent 10 to 12 days after exposure. Measles should be suspected in a patient with the following clinical features whose history indicates susceptibility and exposure (i.e., an unimmunized person with a history of exposure or travel):
- Severe acute respiratory illness. Measles usually presents as an acute respiratory viral illness, which typically lasts 2 to 4 days. The illness involves high fevers, malaise, anorexia, and the “three Cs”: cough, coryza (rhinitis) and conjunctivitis. Patients usually appear sicker than those with more common viral illnesses.
- Koplik spots, which are pathognomonic for measles, are seen in the first few days of illness. They are bluish-white, slightly raised lesions on an erythematous base on the buccal mucosa, usually opposite the first molar. Spots can also be seen on the soft palate, conjunctiva, and vaginal mucosa. Koplik spots usually disappear after a few days and often are not appreciable at the time of evaluation.
Koplik spots (arrow), indicating the onset of measles, in a patient who presented three days before the eruption of skin rash.
- Discrete erythematous patches develop on the face and neck a day after the appearance of Koplik spots. This rash becomes more confluent as it spreads to involve the entire body. It typically lasts for 3 to 7 days, then fades in a similar pattern. The confluent nature of this rash and its spread from the face and neck to the entire body are characteristic of measles. Patients are highly contagious from 4 days before the onset of the rash to 4 days after.
Measles on the third day of rash.
Complications can be severe
Those at highest risk for measles complications are infants, children under age 5, adults over age 20, pregnant women, and immunosuppressed individuals.7
- Pneumonia—either a primary measles pneumonia or a secondary viral or bacterial pneumonia—is the most common cause of death.8,9 Viruses complicating measles are typically adenovirus and herpes simplex virus. Bacteria causing secondary infection are usually Staphylococcus aureus and Streptococcus pneumoniae and, less commonly, gram-negative bacteria.
- Laryngotracheobronchitis (croup) is the second most common cause of death, with bacteria and viruses similar to those causing measles-related pneumonia.
- Otitis media is the most common complication of measles. Other respiratory complications include mastoiditis, pneumothorax and mediastinal emphysema.
- Acute measles encephalitis occurs in one measles case per 1,000 and often results in permanent brain damage. During the convalescent phase of the illness, fever again emerges, with the development of headaches, seizures and altered consciousness.10
- Subacute sclerosing panencephalitis is a rare fatal degenerative disease of the central nervous system caused by a persistent infection with a defective measles virus. The precise pathophysiology is unclear, but it is thought that mutations of the viral genome lead to altered cellular immunity.11 The condition typically occurs seven to ten years after the initial measles infection, particularly in those who developed measles before age 2. Clinical manifestations include behavioral disturbances, intellectual deterioration, and myoclonic seizures, slowly progressing to a vegetative state and death.12 Other complications of measles include diarrhea and stomatitis, which are associated with malnutrition in developing countries, and subclinical hepatitis, thrombocytopenia, appendicitis, ileocolitis, hypokalemia and myocarditis.
- During pregnancy, measles infection can be complicated by primary measles pneumonia and is associated with an increased risk of miscarriage and premature birth.13 Patients with a cell-mediated immunodeficiency who develop measles are particularly susceptible to fatal measles pneumonia and acute progressive encephalitis.14
Laboratory confirmation of measles is recommended for suspected cases. Because viral isolation is technically difficult and is not readily available in most laboratories, measles-specific immunoglobulin M antibody serologic testing is most commonly used. It is almost 100% sensitive when done two to three days after the onset of the rash.15 Measles RNA testing by real-time polymerase chain reaction to detect measles virus in the blood, throat, or urine is more specific and if available may be preferred over serologic testing.16
Supportive management and vitamin A supplementation
No specific antiviral therapy for measles is available. Management involves supportive measures and monitoring for secondary bacterial complications. The World Health Organization and the American Academy of Pediatrics recommend vitamin A supplementation for all children with acute measles.17 In developing countries, it has been shown to reduce rates of morbidity and death in measles-infected children.18 In the United States, children with measles have been found to have low serum levels of vitamin A, with lower levels associated with more severe disease.
- Stokes J Jr, Reilly CM, Buynak EB, Hilleman MR. Immunologic studies of measles. Am J Hyg. 1961;74:293–303.
- Bloch AB, Orenstein WA, Stetler HC, et al. Health impact of measles vaccination in the United States. Pediatrics. 1985;76:524–532.
- Katz SL, Hinman AR. Summary and conclusions: measles elimination meeting, 16-17 March 2000. J Infect Dis. 2004;189(suppl 1):S43–S47.
- McLean HQ, Fiebelkorn AP, Temte JL, Wallace GS; Centers for Disease Control and Prevention (CDC). Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013;62:1–34.
- Clemmons NS, Gastanaduy PA, Fiebelkorn AP, Redd SB, Wallace GS; Centers for Disease Control and Prevention (CDC). Measles—United States, January 4 – April 2, 2015. MMWR Morb Mortal Wkly Rep. 2015;64:373–376.
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- Perry RT, Halsey NA. The clinical significance of measles: a review. J Infect Dis. 2004;189(suppl 1):S4–S16).
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- Quiambao BP, Gatchalian SR, Halonen P, et al. Coinfection is common in measles-associated pneumonia. Pediatr Infect Dis J. 1998;17:89–93.
- Johnson RT, Griffin D, Hirsch R, et al. Measles encephalomyelitis—clinical and immunologic studies. N Engl J Med. 1984;310:137–141.
- Garg RK. Subacute sclerosing panencephalitis. Postgrad Med. J 2002;78:63–70.
- Sever JL. Persistent measles infection of the central nervous system: subacute sclerosing panencephalitis. Rev Infect Dis. 1983;5:467–473.
- Atmar RL, Englund JA, Hammill H. Complications of measles during pregnancy. Clin Infect Dis. 1992;14:217–226.
- Kaplan LJ, Daum RS, Smaron M, McCarthy CA. Severe measles in immunocompromised patients. JAMA. 1992;267:1237–1241.
- Bellini WJ, Helfand RF. The challenges and strategies for laboratory diagnosis of measles in an international setting. J Infect Dis. 2003;187(suppl 1):S283–S290.
- Riddell MA, Chibo D, Kelly HA, Catton MG, Birch CJ. Investigation of optimal specimen type and sampling time for detection of measles virus RNA during a measles epidemic. J Clin Microbiol. 2001;39:375–376.
- Measles. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, editors. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:489-499.
- Huiming Y, Chaomin W, Meng M. Vitamin A for treating measles in children. Cochrane Database Syst Rev. 2005;4:CD001479.
Note: This is an abridged version of an article originally published in the Cleveland Clinic Journal of Medicine.