Measles (rubeola) is a highly contagious viral infection; 90% of nonimmunized persons who come into direct contact with the virus will develop measles. Measles is currently a rare disease in developed countries because of a live vaccine introduced in 1963. Measles, however, still occurs sporadically and in mini-epidemics as well as epidemics in developing nations. The World Health Organization (WHO) estimates that there are 30 million cases of measles worldwide that result in 888,000 deaths, reflecting that measles remains a significant cause of morbidity and mortality. In 1989, the WHO set a goal of vaccinating 90% of children worldwide against measles by the year 2000; they succeeded by targeting elimination in particular geographic locations. They estimate near global elimination of epidemic measles by the year 2007.

Measles, a morbillivirus of the paramyxovirus family, is spread by direct contact with infectious droplets from the nose, mouth, or throat or by airborne spread. Lifelong immunity is conferred by one attack of measles. Although most cases result from a failure to immunize, some patients fail to seroconvert after one-dose vaccination (primary vaccine failure), while others experience waning immunity from immunizations in childhood (secondary vaccine failure). Atypical measles—an often severe illness resulting in fever, interstitial pulmonary infiltrates, hepatitis, edema of the extremities, and pleural effusion—is associated with exposure to the virus following vaccination with killed virus; this product was removed from the United States market in 1967 and the Canadian market in 1970. Atypical measles is thought to be induced by hypersensitivity following exposure to the inactivated vaccine.

• Impaired cell-mediated immunity (e.g., patients with cellular immune defects, human immunodeficiency virus [HIV] or patients receiving either chemotherapy or immunosuppressive medication)
• Infants less than 1 year of age as they are too young to be immunized
• Children and adults who have not been immunized
• One-dose immunization (before 1989 when two-dose immunization became the rule), resulting in a lack of seroconversion
• 15 years following immunization with live vaccine, immunity wanes in rare instances

• Malaise
• Fever (moderate to high) for up to 5 days
• Conjunctivitis
• Cough including croup; often manifests as bronchitis or pneumonia
• Laryngitis
• Coryza
• Photophobia
• Enanthema (red spots with bluish-white center, Koplik's spots) on oral mucosa
• Spreading erythematous, maculopapular skin rash, usually beginning at hairline or behind the ears; spreads to trunk and limbs; may include palms and soles
• Diarrhea
• Vomiting
• Lymphadenopathy
• CNS symptomatology -- 1 in 1,000 cases including headache, drowsiness, coma, and/or seizures

• Rubella (German measles)
• Roseola infantum
• Erythema infectiosum (fifth disease)
• Infectious mononucleosis
• Kawasaki disease
• Scarlet fever
• Toxoplasmosis
• Drug eruption
• Differential for atypical measles—includes Rocky Mountain spotted fever, Henoch-Schönlein purpura, and meningococcemia

The classic presentation is a severe upper respiratory infection, after which Koplik's spots, which are pathognomonic, appear on the oral mucosa. The classic measles rash appears several days after the Koplik's spots disappear.

• Neutropenia, particularly lymphopenia, are common secondary to invasion of virus into leukocytes with subsequent cell death
• Leukocytosis may be a sign of bacterial superinfection
• Immunofluorescent staining of nasopharyngeal or respiratory secretions—to detect measles antibodies and/or multinucleated giant cells
• Enzyme immunoassay (EIA)—to detect IgM (present within 1 to 2 days of rash) or IgG antibodies (rises after 10 days); atypical measles is associated with very high antibody titers
• Hemagglutination inhibition test—to detect IgM or IgG antibodies; older test; not as sensitive as EIA
• In the case of CNS symptoms, lumbar puncture is performed; in the case of measles encephalitis, CSF reveals elevated protein and lymphocytosis

Measles virus first attacks the respiratory system and spreads to the reticuloendothelial system via the bloodstream. When it infects the leukocytes, it results in primary viremia, with systemic spread to many organs and tissues. T-cell invasion may account for the depressed cellular immunity of measles. Cellular immunity (including cytotoxic T cells and natural killer cells) plays a prominent role in the host's defense against measles.

• Electroencephalogram—to determine extent of CNS involvement
• Polymerase chain reaction—to detect measles virus RNA

Treatment for measles is symptomatic and supportive; however, complications may indicate specific treatment and hospitalization which is common in certain parts of the world. If encephalitis ensues, the patient must be observed because of the risk of increased intracranial pressure.

• Antipyretics for the management of high fevers
• Antibiotics for the management of bacterial complications such as pneumonia and otitis media
• High-dose vitamin A, 50,000 IU for infants 1 to 6 months; 100,000 IU for infants 7 to 12 months; and 200,000 IU for children over 1 year; given for 2 days particularly for severe measles in malnourished children. May see transient vomiting and headache with high doses of vitamin A. See section entitled Nutrition for more information regarding use of vitamin A in the case of measles.
• Ribavirin has demonstrated antiviral activity in vitro and may be considered for immunocompromised host, although not FDA-approved for measles.
• Postexposure prophylaxis: immune globulin, 0.25 ml/kg (0.5 ml/kg for immunocompromised patients) IM within 6 days of exposure followed by immunization in 5 to 6 months. (Caution: immune globulin should not be given at the same time as the vaccine.) The vaccine may also be used for post-exposure prophylaxis within 72 hours; the vaccine is not as effective for these purposes as immunoglobulin; also, vaccine should not be used in immunocompromised individuals.

Studies have demonstrated the importance of nutrient supplementation in the treatment of measles, specifically supplementation with vitamin A (sometimes called the "anti-infective" vitamin). Herbs have been used worldwide to treat measles and there is mounting evidence of their benefit. Some folk remedies, such as the Cherokee use of spicebush (Lindera benzoin), have been used traditionally for measles but have yet to be scientifically investigated. Constituents include benzoin, aromatic hydrocarbons, and aporphines, which possess cytotoxic properties (McWhorter 1996).

Vitamin A

Vitamin A deficiency is a critical problem among populations commonly lacking adequate dietary intake. This nutrient deficiency is associated with greater frequency, severity, and mortality of infectious diseases, including measles. In areas of the world where vitamin A deficiency is endemic or where fatality from measles occurs at a rate of 1% or higher, the WHO recommends routine vitamin A supplementation for children with the infection (Hussey and Klein 1990). This recommendation is based upon and supported by randomized, controlled clinical trials demonstrating a benefit of vitamin A supplementation including the following outcomes (Coutsoudis et al. 1991; Hussey and Klein 1990):

• Reduction in mortality rate by > 50% 
• Decreased duration of pneumonia and diarrhea by > 30% 
• Shorter length of hospital stay by > 30% 

Flavonoids

Flavonoids are known to exhibit a variety of activities, including:

• Peripheral vasodilation 
• Inhibition of lipid peroxidation
• Antiviral activities

A series of flavonoids isolated from the following herbs were tested in vitro against several viruses: 

• Rhus succedanea L. (Wax tree) 
• Garcinia multiflora

Rhusflavanone demonstrated slight, reportedly significant, anti-measles activity (Lin et al. 1999).

• Calendula officinalis (Calendula flower) has demonstrated anti-viral activity in vitro and is thought to have immune-enhancing properties; although, this herb has not been studied against measles specifically (Blumenthal et al. 2000).

Herbal Combination Remedies

Researchers report that the Chinese herbal formula Shengma-gegen-tang exhibits anti-measles activity in vitro by selectively stimulating secretion of TNF-alpha in peripheral blood mononuclear cells (PBMN). In one study, PBMN cells (taken from healthy donors) were inoculated with a measles virus and exposed to various concentrations of Shengma-gegen-tang, containing:

• Cimicifugae racemosa (Black cohosh) 
• Pueraria lobata Ohwi (Kudzu vine) 
• Paeoniae lactiflora (Peony root) 
• Zingiber officinale (Ginger root)
• Glycyrrhizae glabara (Licorice root)

The combination herbal remedy showed significant cytotoxicity against the measles virus in the PBMN cells. The authors speculate that this formula acts by enhancing the immune system rather than by suppressing the growth of the measles virus (Huang et al. 1997).

In vitro studies of 142 extracts of traditional herbal remedies studied found the following to have anti-measles activity (Kurokawa et al. 1993):

• Artemisia princeps (Mugwort) 
• Brucea javanica (Kosam seed) 
• Caesalpinia sappan (Sappan wood) 
• Coptis chinensis (Goldthread) 
• Elaeocarpus grandiflorus 
• Forsythia suspensa (Forsythia) 
• Phellodendron amurense (Amur corktree) 
• Punica granatum (Pomegranate) 
• Rhus javanica (Japanese sumac) 
• Scutellaria baicalensis (Chinese Skullcap) 
• Woodfordia floribunda (Fire-flame bush) 

More research is needed to assess whether these pharmacologic properties have clinical relevance.

Measles is most often an uncomplicated childhood illness; however, infants and adults, especially those who are immunocompromised, malnourished, or otherwise debilitated, often develop complications that require hospitalization.

Live attenuated measles vaccine, available as the combination vaccine of measles-mumps-rubella (MMR) is administered in two doses—one at 12 to 15 months (preferably at 12 months if mother received childhood vaccine and never had the disease) and the second at either 4 to 5 or 12 years (the former is recommended by the CDC and the latter by the American Academy of Pediatrics). The two-dose regimen was instituted in the 1980's in response to an outbreak at that time. Vaccine confers lifelong immunity in 95% of recipients. Adults who have received only one vaccination, or who were vaccinated as children, often have low antibody titers and may need to be revaccinated. (Caution: patients with egg or neomycin allergies may experience anaphylaxis as vaccine virus is grown in chick embryos.) Individuals born prior to 1957 who are at risk for measles exposure should have antibodies tested and be immunized if necessary. Ten percent of immunocompetent vaccine recipients develop fever and rash 5 to 7 days following vaccination. Following use of immunosuppresent medications, the vaccine should not be administered for at least 3 months.

• Respiratory system complications: otitis media, croup, bronchiolitis, pneumonia (accounts for 60% of deaths in infants), worsening of tuberculosis (TB) or activation of a latent TB infection
• Activation of herpes simplex virus
• Central nervous system complications: encephalomyelitis (0.1% of patients), resulting in mental retardation, epilepsy, or death (10% to 15% of patients); subacute sclerosing panencephalitis (a rare but severe form of measles encephalitis due to persistent infection with a measles-related virus in the CNS), cerebellar ataxia, neuritis, hemiplegia
• Gastrointestinal complications: gastroenteritis, appendicitis, hepatitis, ileocolitis, mesenteric adenitis
• Other: glomerulonephritis, myocarditis, postinfectious thrombocytopenic purpura

Most cases of measles resolve without sequelae; however, mortality is higher among immunocompromised individuals, the elderly, and children younger than 2 years of age. The measles mortality rate is 0.3% in industrialized countries, and 1% to 10% in developing countries. Individuals who contract subacute sclerosing panencephalitis (usually 10 years after contracting measles) generally will die within 2 years.

Measles in pregnancy is not teratogenic (as is rubella); however, measles in a pregnant woman can be severe and result in prematurity, miscarriage, stillbirth, or low birth weight. Infants of mothers with active measles should be given immune globulin at birth; their measles can be mild or severe. Pregnant women should not be vaccinated.

Anonymous. Global measles control and regional elimination, 1998–1999. MMWR Morb Mortal Wkly Rep. 1999;48(49):1124-1130.

Beers MH, et al. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2320-2324.

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, Mass: Integrative Medicine Communications; 1998.

Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Boston, Mass: Integrative Medicine Communications; 2000:44-46.

Bove M. An Encyclopedia of Natural Healing for Children and Infants. New Canaan, Conn: Keats Publishing Inc.; 1996:165-167.

Coutsoudis A, Broughton M, Coovadia HM. Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial. Am J Clin Nutr. 1991;54(5):890-895.

Fauci AS, Braunwald E, Isselbacher KJ, et al. Harrison's Principles of Internal Medicine. Vol. 1. 14th ed. New York, NY: McGraw-Hill Book Co. 1998;1123-1125.

Huang SP, Shieh GJ, Lee L, Teng HJ, Kao ST, Lin JG. Inhibition effect of Shengma-gegen-tang on measles virus in Vero cells and human peripheral blood mononuclear cells. Am J Chin Med. 1997;25(1):89-96.

Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. N Engl J Med. 1990;323(3):160-164.

Kelly WN, et al. Textbook of Internal Medicine. Vol. 2. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1997:1758-1760.

Kurokawa M, Ochiai H, Nagasaka K, et al. Antiviral traditional medicines against herpes simples virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice. Antiviral Res. 1993;22(2-3):175-188.

Lin YM, Flavin MT, Schure R, et al. Antiviral activities of bioflavonoids. Planta Med. 1999;65(2):120-125.

Mandell GL, et al. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone; 1995:1519-1524.

McWhorter JH. Spicebush: a Cherokee remedy for the measles. N C Med J. 1996;57(5):306.

Murray PR, et al. Manual of Clinical Microbiology. 7th ed. Washington, DC: ASM Press; 1999:951-957.

Rakel RE. Latest Approved Methods of Treatment for the Practicing Physician. Philadelphia, Pa: W.B. Saunders Co; 1999:136-138.

Rosen P, et al. Emergency Medicine: Concepts and Clinical Practice. Vol. 3. 4th ed. St. Louis, Mo: Mosby; 1998:2546-2547.

Taylor RB, et al. Family Medicine: Principles and Practice. 5th ed. New York: NY: Springer-Verlag; 1998:170-171.