Measles(Rubeola; Morbilli; 9-Day Measles) http://www.merck.com/mmpe/sec14/ch193/ch193b.

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Measles is a highly contagious, viral infection that is most common among children. It is characterized by fever, cough, coryza, conjunctivitis, enanthem (Koplik's spots) on the buccal or labial mucosa, and a maculopapular rash that spreads cephalocaudally. Diagnosis is usually clinical. Treatment is supportive. Vaccination is highly effective. Worldwide, measles infects about 20 million people causing about 200,000 deaths annually, primarily in children. Measles is rare in the US because of routine childhood vaccination; an average of 63 cases/yr were reported to the Centers for Disease Control and Prevention (CDC) from 2000 to 2007. However, in 2008, 131 cases were reported from January to July. Pathophysiology 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 h 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 had measles receives antibodies transplacentally; these antibodies are protective for most of the first 6 to 12 mo of life. Lifelong immunity is conferred by infection. In the US, many measles cases are imported by travelers or immigrants; indigenous transmission occurs primarily among unvaccinated people. Symptoms and Signs After a 7- to 14-day incubation period, measles begins with a prodrome of fever, coryza, hacking cough, and tarsal conjunctivitis. The pathognomonic Koplik's spots appear 2 to 4 days later, usually on the buccal 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 buccal mucosa. Sore throat develops. Rubeola (Koplik's Spots)

The rash appears 3 to 5 days after symptom onset, usually 1 to 2 days after Koplik's 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 h, 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. Rubeola (Diffuse Macular Rash)

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: Complications include

Atypical measles syndrome Pneumonia Bacterial superinfection Acute thrombocytopenic purpura Encephalitis Subacute sclerosing panencephalitis

Atypical measles syndrome usually occurs in people previously immunized with the original killed-virus measles vaccines, which have been unavailable since

1968. The older vaccines can alter disease expression after infection with wildtype measles. Atypical measles syndrome may begin abruptly, with high fever, prostration, headache, abdominal pain, and cough. The rash may appear 1 to 2 days later, often beginning on the extremities, and may be maculopapular, vesicular, urticarial, or purpuric. Edema of the hands and feet may occur. Pneumonia and hilar adenopathy are common and may be prolonged; chest x-ray abnormalities may persist for weeks to months. Symptomatic hypoxemia may occur. Pneumonia 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 and otitis media. Measles transiently suppresses delayed hypersensitivity, which can worsen active TB 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, although occasionally bleeding is severe. Encephalitis occurs in 1/1000 to 2000 cases, usually 2 days to 2 wk after onset of the rash, often beginning with recrudescence of high fever, headache, seizures, and coma. CSF usually has a lymphocyte count of 50 to 500/L and a mildly elevated protein level but may be normal initially. Encephalitis may resolve in about 1 wk or may persist longer, causing morbidity or death. Transient hepatitis may occur during an acute infection. Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, ultimately fatal, late complication of measles (see Other Viruses: Subacute Sclerosing Panencephalitis (SSPE)). Diagnosis

Clinical evaluation Serologic testing Viral detection via culture or reverse transcriptionPCR

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's spots or the rash. CBC is unnecessary but, if obtained, may show leukopenia with a relative lymphocytosis. Laboratory identification 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 reverse transcriptionPCR 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, scarlet fever, drug rashes (eg, from phenobarbital Some Trade Names LUMINAL Click for Drug Monograph or sulfonamides), serum sickness, roseola infantum, infectious mononucleosis, erythema infectiosum (see Miscellaneous Infections in Infants and Children: Erythema Infectiosum), and echovirus and coxsackievirus infections (see also Table 1: Viruses: Some Respiratory Viruses ). Atypical measles, because of its greater variability, can simulate even more conditions than typical measles. 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 yr. Initial temperature is usually high, Koplik's spots and malaise are absent, and defervescence and rash occur simultaneously.

Prognosis Mortality is about 2/1000 in the US but is much higher in the developing world. Undernutrition and vitamin A deficiency may predispose to mortality. Vitamin A supplementation is recommended for populations at risk. Treatment

Supportive care For children, vitamin A

Treatment is supportive, including for encephalitis. Vitamin A supplementation has been shown to reduce morbidity and mortality due to measles in children in the developing world. 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/day for 2 days and depends on the child's age:

> 1 yr: 200,000 international units (IU)

6 to 11 mo: 100,000 IU < 6 mo: 50,000 IU

In children with clinical signs of vitamin A deficiency, a single age-specific dose of vitamin A is repeated 2 to 4 wk later. Prevention A live-attenuated virus vaccine containing measles, mumps, and rubella is routinely given to children in most developed countries (see also Immunization: Measles, Mumps, and Rubella; see Table 10: Approach to the Care of Normal Infants and Children: Recommended Immunization Schedule for Ages 06 yr ). The first dose is recommended at age 12 to 15 mo but can be given as young as age 6 mo during a measles outbreak. Two doses are recommended; the second is given at age 4 to 6 yr. Infants immunized at < 1 yr of age still require 2 further 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% of vaccinees and can be followed by a rash. CNS reactions are exceedingly rare; the vaccine does not cause autism. 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 TB, or 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 mo. Postexposure prophylaxis: Prevention in susceptible contacts is possible by giving the vaccine within 3 days of exposure. If vaccine should be deferred, immune globulin 0.25 mL/kg IM (maximum dose, 15 mL) is given immediately, with vaccination given 5 to 6 mo later if medically appropriate (eg, if patient is no longer pregnant). An exposed immunodeficient patient with a contraindication to vaccination is given immune globulin 0.5 mL/kg IM (maximum, 15 mL). Immune globulin should not be given simultaneously with vaccine. Last full review/revision November 2009 by Mary T. Caserta, MD Content last modified November 2009

Introduction
Background
Measles virus (MV), a negative-sense enveloped RNA virus, is a member of the Morbillivirus genus in the Paramyxoviridae family. Measles is a highly communicable acute disease. It is also known as rubeola and is marked by prodromal fever, cough, coryza, conjunctivitis, and pathognomonic enanthem (ie, Koplik spots), followed by an erythematous maculopapular rash on the third to seventh day. Infection confers life-long immunity. A generalized immunosuppression that follows acute measles frequently predisposes patients to bacterial otitis media and bronchopneumonia. In approximately 0.1% of cases, measles causes acute encephalitis. Subacute sclerosing panencephalitis (SSPE) is a rare chronic degenerative disease that occurs several years after measles infection. Because of a failure to deliver at least one dose of measles vaccine to all infants in certain industrialized and developing nations, measles remains a common disease in certain regions and continues to account for nearly 50% of the 1.6 million deaths caused each year by vaccine-preventable childhood diseases. Maternal antibodies play a significant role in protection against infection in infants younger than 1 year and may interfere with live-attenuated measles vaccination. A single dose of measles vaccine administered to a child older than 12 months induces protective immunity in 95% of recipients. Because measles virus is highly contagious, a 5% susceptible population is sufficient to sustain periodic outbreaks in otherwise highly vaccinated populations. A second dose of vaccine, now recommended for all school-aged children in the United States,1 induces immunity in about 95% of the 5% who do not respond to the first dose. Slight genotypic variation in recently circulating strains has not affected the protective efficacy of liveattenuated measles vaccines. Unsubstantiated claims that suggest an association between the measles vaccine and autism have resulted in reduced vaccine use and a recent resurgence of measles in countries where immunization rates have fallen to below the level needed to maintain herd immunity.2,3 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 people in both developed and developing countries must be sustained. Vitamin A supplementation during acute measles significantly reduces risks of morbidity and mortality.

Pathophysiology
In temperate areas, the peak incidence of infection occurs during late winter and spring. Measles virus is spread by direct contact via respiratory droplets or, less commonly, by airborne transmission. Initial infection and viral replication occur locally in tracheal and bronchial epithelial cells. After 2-4 days, measles virus infects local lymphatic tissues, perhaps carried by pulmonary macrophages. Following the amplification of measles virus in regional lymph nodes, a predominantly cell-associated viremia disseminates the virus to various organs prior to the appearance of rash. In individuals with deficiencies in cellular immunity, measles virus causes a progressive and often fatal giant cell pneumonia. Measles virus infection causes an immunosuppression marked by decreases in delayed-type hypersensitivity, interleukin-12 production, and antigen-specific lymphoproliferative responses that persist for weeks to months after the acute infection. Immunosuppression may predispose individuals to severe bacterial infection, particularly bronchopneumonia, a major cause of measles-related mortality among younger children.

Frequency
United States The practice of administering 2 doses of live-attenuated measles vaccine to children to prevent school outbreaks of measles was implemented when the vaccine was first licensed in 1963. The immunization program resulted in a decrease of more than 99% in reported incidence. The last major US outbreak (1989-1991) affected more than 55,000 Americans and resulted in 123 deaths. Vaccination programs interrupted the transmission of indigenous measles virus in the United States by 1993 and reduced the incidence of measles to an historic low (<0.5 cases per million persons) by 1997-1999. From 1997-2004, the reported incidence was as low as 37116 cases per year. Since November 2002, measles has not been considered an endemic disease in the United States. Despite the highest recorded immunization rates in history, young children who are not appropriately vaccinated may experience more than a 60-fold increase in risk of disease due to exposure to imported measles cases from countries that have not yet eliminated the disease. In 2006, a total of 49 confirmed cases were reported in United States. International Approximately 30 million measles cases are reported annually. Most reported cases are from Africa. In 1998, the cases of measles per 100,000 total population reported to the World Health Organization was 1.6 in the Americas, 8.2 in Europe, 11.1 in the Eastern

Mediterranean region, 4.2 in South East Asia, 5.0 in the Western Pacific region, and 61.7 in Africa. Only 187 confirmed cases were reported in the Western Hemisphere (mainly in Venezuela, Mexico, and the United States) in 2006.4

Mortality/Morbidity
Common infectious complications include otitis media, interstitial pneumonitis,5 bronchopneumonia, laryngotracheobronchitis (ie, croup), exacerbation of tuberculosis, transient loss of hypersensitivity reaction to tuberculin skin test, encephalomyelitis, and diarrhea. Rare complications include hemorrhagic measles, purpura fulminans, hepatitis, disseminated intravascular coagulation (DIC), and SSPE. Transient hepatitis may occur during an acute infection. Approximately 1 of every 1,000 patients develops acute encephalitis, which often results in permanent brain damage. SSPE, a degenerative CNS disease, can result from a persistent measles infection. SSPE is characterized by the onset of behavioral and intellectual deterioration and seizures years after an acute infection (the mean incubation period for SSPE is approximately 10.8 years). Measles is still a leading cause of death among children, despite the availability of an effective vaccine. Measles-related mortality, most often due to respiratory and neurologic complications, occurs in 0.1-0.3% of reported US cases. Measles caused an estimated 197,000 deaths worldwide in 2007.4 An estimated 85% of these deaths occur in Africa and Southeast Asia. Case-fatality rates are higher among children younger than 5 years. Highest fatality rates are among infants aged 4-12 months and in children who are immunocompromised because of human immunodeficiency virus (HIV) infection or other causes. From 2000-2007, deaths worldwide fell by 74% (from an estimated 750,000 to 197,000), thanks to the partnership of several global organizations.

Race
Measles affects people of all races.

Sex
Excess mortality following acute measles has been observed among females at all ages, but it is most marked in adolescents and young adults. Excessive nonmeasles-related mortality has also been observed among female recipients of high-titer measles vaccines in Senegal, Guinea Bissau, and Haiti.6

Age
Unvaccinated young children are at the highest risk. Age-specific attack rates may be highest in susceptible infants younger than 12 months, school-aged children, or young adults, depending on local immunization practices and incidence of the disease. Complications such as otitis media, bronchopneumonia, laryngotracheobronchitis (ie, croup), and diarrhea are more common in young children.

Clinical
History

The incubation period from exposure to onset of measles symptoms ranges from 8-12 days. The first sign of measles is usually a high fever that usually last 4-7 days. The prodromal phase is marked by malaise, fever, anorexia, and conjunctivitis, cough, and coryza (the "3 Cs"). Small white spots inside the cheeks can be seen during the early stage, prior to eruption of rash (see image below).

Koplik spots in measles. Photograph courtesy of the World Health Organization (WHO). [ CLOSE WINDOW ]

Koplik spots in measles. Photograph courtesy of the World Health Organization (WHO).

Rash usually occurs, on average, 14 days after exposure and starts on the face and upper neck and spreads to extremities (see image below).

Child with measles. Photograph courtesy of the Centers for Disease Control and Prevention (CDC). [ CLOSE WINDOW ]

Child with measles. Photograph courtesy of the Centers for Disease Control and Prevention (CDC).

The entire course of uncomplicated measles, from late prodrome to resolution of fever and rash, is 7-10 days. Cough may be the final symptom to appear. Patients are contagious from 1-2 days before onset of symptoms. Healthy children are also contagious during the period from 3-5 days before the appearance of the rash to 4

days after the onset of rash. On the other hand, immunocompromised individuals can be contagious during the duration of the illness.

Physical

Fever: A temperature often exceeding 104F (40C) begins with the prodrome and persists 7-10 days. Enanthem: Koplik spots (ie, bluish-gray specks or "grains of sand" on a red base) appear on the buccal mucosa opposite the second molars near the end of the prodrome. It is generally seen 2 days prior to the appearance of the rash and lasts until 2 days after the rash appears (see image below). This enanthem begins to slough as the rash appears. Although this is the pathognomonic enanthem of measles, its absence does not exclude diagnosis.

Koplik spots in measles. Photograph courtesy of the World Health Organization (WHO). [ CLOSE WINDOW ]

Koplik spots in measles. Photograph courtesy of the World Health Organization (WHO).

Rash: An erythematous and maculopapular rash that becomes confluent begins on the face and then proceeds to the trunk, extremities, palms, and soles; it lasts for about 5 days. Patients appear most ill during the first or second day of the rash. Desquamation and brown staining, which spares the palms and soles, may occur after one week. The rash may be absent in patients with underlying deficiencies in cellular immunity. Lymphoid involvement: Generalized lymphadenopathy, mild hepatomegaly, and appendicitis may occur because of generalized involvement of lymphoid tissue.

Causes
The highly contagious measles virus is spread by coughing and sneezing via close personal contact or direct contact with secretions.

Risk factors for infection o Children with immunodeficiency due to HIV or acquired immunodeficiency syndrome (AIDS), leukemia, alkylating agents, or corticosteroid therapy, regardless of immunization status
o

Travel to areas where measles is endemic or contact with travelers to endemic areas Infants who lose passive antibody prior to the age of routine immunization

Risk factors for severe measles and its complications

o

Malnutrition

o o o

Underlying immunodeficiency Pregnancy Vitamin A deficiency

Differential Diagnoses
Dengue Parvovirus B19 Infection Drug Eruptions Pediatrics, Roseola Infantum Enteroviral Infections Pediatrics, Scarlet Fever Infectious MononucleosisRocky Mountain Spotted Fever Kawasaki Disease Rubella Meningococcemia Toxic Shock Syndrome

Workup
Laboratory Studies
Diagnosis of measles is usually determined from the classic clinical picture.

Confirmation of measles virus (MV) infection o The measles virus sandwich-capture immunoglobulin M (IgM) antibody assay is the quickest method to confirm acute measles. Because IgM may not be detectable during the first 2 days of rash, obtain blood for measles-specific IgM on the third day of the rash or on any subsequent day up to one month after onset to avoid a false-negative IgM result. Among persons with confirmed measles infection, the seropositivity rate for first samples is about 77% when collected within 72 hours; the rate rises to 100% when collected 411 days after rash onset.7 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 subjects at 4 weeks after rash onset. The assay is offered through many local health departments and through the Centers for Disease Control and Prevention (CDC).
o

Laboratories can confirm measles by demonstrating more than a 4-fold rise in immunoglobulin G (IgG) antibodies between acute and convalescent sera. 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. Thus, take specimens on the seventh day after rash onset and repeat 10-14 days later to confirm the case as soon as possible. Patients with subacute sclerosing panencephalitis (SSPE) have unusually high titers of measles antibody in their serum and cerebrospinal fluid. The earliest confirmation of measles using IgG antibodies takes about 3 weeks from the onset of illness, a delay too long to permit implementation of effective control measures. Measles virus can be isolated from nasopharyngeal swabs. Viral genotyping in a reference laboratory may determine whether an isolate is endemic or imported. In immunocompromised patients, who may have poor antibody responses that preclude serologic confirmation of measles, virus isolation from

infected tissue or identification of measles antigen by immunofluorescence may be the only method to confirm the diagnosis.

Other diagnostic tests

o

A leukopenia with a relative lymphocytosis occurs in the late stages of viremia. Elevated hepatic transaminase levels may be detected in patients with measles virus hepatitis.

Imaging Studies

Perform chest radiography if bacterial pneumonia is suspected. The frequent occurrence of measles pneumonia, even in uncomplicated cases, limits the predictive value of chest radiography for bacterial bronchopneumonia.

Other Tests

Perform a lumbar puncture if encephalitis is suspected. Cerebrospinal fluid examination reveals the following:
o o o

Increased protein Normal glucose Mild pleocytosis with a predominance of lymphocytes

Histologic Findings

Lymphoid multinucleated giant cells ( 100 nm in diameter) can be identified in biopsies of Koplik spots, in dermal or epithelial rashes, and in lung or lymphoid tissue. Brain biopsies of patients with measles encephalitis can reveal demyelination, vascular cuffing, gliosis, and infiltration of fat-laden macrophages near blood vessel walls.

Treatment
Medical Care

Treatment of measles is essentially supportive. Vitamin A supplements have been associated with reduction in morbidity and mortality (by 50%) and are recommended in the following children:8
o o o

Those who live in developing countries or in areas of impoverishment in developed countries Children aged 6-24 months who are hospitalized for measles-related complications Those with immunodeficiency

o o o o

Those with evidence of an ophthalmologic complication due to vitamin A deficiency Children with malnutrition Children with impaired intestinal absorption Those who have recent emigrated from an area with high mortality rates due to measles

Consider antibiotic or ribavirin (experimental) administration if evidence suggests otitis media or bacterial pneumonia. To prevent or modify measles in exposed susceptible individuals, consider administering measles virus (MV) vaccine or human immunoglobulin (Ig). The morbidity rate is high in children younger than 1 year; therefore, Ig is recommended in these patients. The Measles virus vaccine is routinely administered as measles-mumpsrubella (MMR) in two doses. For more information, see the 2009 CDC immunization schedule for children aged birth through 18 years.1
o o

The first dose is given to healthy individuals on or after age 1 year. The second dose is given upon school entry, usually at age 46 years.

Ig is given to the following individuals:

o o o o

Those with immunocompromise Infants aged 6 months to 1 year Infants younger than 6 months who are born to mother without measles immunity Pregnant women

Consultations

Consult public health or infectious disease specialists for recommendations and guidelines for diagnostic confirmation of cases and prophylaxis of susceptible contacts.

Diet

Consider vitamin A supplementation.

Medication
Vitamins
Vitamin A treatment for children with measles in developing countries has been associated with a marked reduction in morbidity and mortality. The World Health Organization (WHO)

recommends vitamin A administration to all children with measles in communities where vitamin A deficiency is a recognized problem and where the measles virus (MV)-related mortality rate exceeds 1%. Of note, low serum concentrations of vitamin A are found in children with severe measles in the United States. Thus, consider supplemental vitamin A in patients aged 6 months to 2 years who are hospitalized with measles and its complications (eg, croup, pneumonia, diarrhea). Two doses of vitamin A given 24 hours apart are recommended. Also recommend vitamin A supplementation for children who have any of the following:

Immunodeficiency Clinical evidence of vitamin A deficiency (eg, ophthalmologic complications) Moderate-to-severe malnutrition, including eating disorders Impaired intestinal absorption Recent emigration from an area with high mortality rates due to measles

Vitamin A (Aquasol A) Fat-soluble vitamin needed for growth of skin, bones, and male and female reproductive organs.

Dosing Interactions Contraindications Precautions

Adult Pediatric

<6 months: Not established 6 months to 1 year: 100,000 IU PO as a single dose; repeat dose the next day and at 4 wk for ophthalmologic evidence of vitamin A deficiency >1 year: 200,000 IU PO as a single dose; repeat dose the next day and at 4 wk for ophthalmologic evidence of vitamin A deficiency

Dosing Interactions Contraindications Precautions

Cholestyramine or neomycin retard absorption

Dosing Interactions Contraindications Precautions

Documented hypersensitivity; large doses may be teratogenic and, thus, contraindicated in pregnancy

Dosing Interactions Contraindications Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions

A 200,000 IU dose may be associated with vomiting and headache; patients with hepatic dysfunction have increased susceptibility to vitamin A toxicity

Antivirals
Measles virus is susceptible to ribavirin in vitro. Although ribavirin (either IV or aerosolized) has been used to treat severely affected and immunocompromised adults with acute measles or SSPE (IV plus intrathecal high-dose interferon-alfa),9 no controlled trials have been conducted; ribavirin is not approved by the Food and Drug Administration (FDA) for this indication, and such use should be considered experimental.

Ribavirin (Virazole) For experimental use only. A guanosine analog, the mechanism of action is not fully defined but relates to alteration of cellular nucleotide pools and of viral messenger RNA information.

Dosing Interactions Contraindications Precautions

Adult

20-35 mg/kg/d IV for 7 d

Pediatric

Not established

Dosing Interactions Contraindications Precautions

Interacts with thymidine-phosphorylated nucleoside analogs (eg, zidovudine, d4T), decreasing their effects

Dosing Interactions Contraindications Precautions

Documented hypersensitivity

Dosing Interactions Contraindications Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Closely monitor patients with COPD and asthma for deterioration of respiratory function; associated with a dose-dependent hemolytic anemia

Vaccines
These agents are available in the United States with attenuated rubella and mumps viruses as the MMR vaccine. For information regarding vaccines and immunization schedules, see the CDC Web site. Several measles vaccines are available in the US, as follows:

Live measles virus vaccine (Attenuvax) Live measles mumps, and rubella virus vaccine (M-M-R II) Live measles, mumps, rubella, and varicella virus vaccine (ProQuad)

Claims that suggest an association between measles vaccine and pervasive developmental or other neurologic disorders have not been substantiated.3 Vaccines are used for universal

immunization of children older than 12 months in the United States or in children at age 9 months in developing countries with high endemicity. In the United States, a second dose can be administered as soon as 2 months later but is generally administered at age 4-6 years. All adults born after 1957 should receive a second dose of MMR unless they are documented as seropositive for measles IgG antibody by enzyme immunoassay (EIA). If administered within 72 hours of exposure to measles-naive individuals, MMR may prevent or attenuate disease. In a susceptible household contact, consider Ig instead. In the United States, 48 states and the District of Columbia require a second dose of measles vaccine for school enrollment. Rates of seroconversion average 85% after a single dose at age 9 months (the recommended strategy for routine immunization in developing countries), 95% after a single dose at 12 months, 98% after a single dose at age 15 months, and greater than 99% after 2 doses administered after age 12 months. The American Academy of Pediatrics suggests an interval of at least 5-6 months after intramuscular Ig (IGIM) is administered before administering the measles vaccine.8

Measles, mumps, and rubella vaccine (M-M-R II) Used to induce immunity against viruses that cause measles, mumps, and rubella.

Dosing Interactions Contraindications Precautions

Adult

0.5 mL SC in outer aspect of upper arm Birth date before 1957: Considered to be immune to measles and mumps, no further MMR vaccination required Birth date during 1957 or later: Should receive >1 dose unless they have a medical contraindication, documentation of >1 dose, history of confirmed measles infection, or laboratory evidence of immunity Second dose recommended for the following adults: (1) those who have been recently exposed to measles or mumps in an outbreak setting, particularly if in their age group; (2) those who have been previously vaccinated with killed measles vaccine; (3) those who have been vaccinated with an unknown type of measles vaccine during 19631967; (4) those who are students in postsecondary educational institutions; (5) those who work in a health care facility; and (6) those who plan to travel internationally Unreliable rubella vaccination history: Administer 1 dose Unvaccinated health care workers born before 1957: If no evidence of mumps immunity; administer 1 dose; strongly consider a second dose during an outbreak situation

Pediatric

First dose: 0.5 mL SC initiated at age >12 months (preferably >15 mo) Second dose: 0.5 mL at age 4-6 y; may be administered before age 4-6 y, provided >4 wk have elapsed since the first dose Catch up doses: If not previously vaccinated by age 6 years, administer 2 doses of 0.5 mL SC with >4 wk between doses

Dosing Interactions Contraindications Precautions

Drugs that suppress immune system may diminish response to immunization; do not administer concurrently with IGIM (must wait at least 5-6 mo after IGIM)

Dosing Interactions Contraindications Precautions

Documented hypersensitivity to vaccine or components (contains neomycin); cancer affecting bone marrow or lymphatic systems, blood dyscrasias, HIV, or other severe immunosuppressive condition; pregnant women or women who might become pregnant within 4 wk of receiving vaccine; for more information, see CDC Guide to Vaccine Contraindications and Precautions

Dosing Interactions Contraindications Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Contraception in females is advised for 3 mo following immunization; not indicated for severely immunocompromised patients; determine rubella immunity for women of childbearing years and counsel regarding congenital rubella syndrome

Immunoglobulins
Human Ig prevents or modifies measles in susceptible individuals if administered within 6 days of exposure.

Immune globulin, intramuscular (GamaSTAN S/D) Transient source of IgG. Indicated for all susceptible contacts of patients with measles who reside in the same household who are pregnant, immunocompromised, or aged 6-12 mo; also indicated for infants less than 6 mo who were born to mothers without measles immunity and also all children and adolescents with HIV infection who are exposed to measles, regardless of measles immunization status, unless they have received IGIV (400 mg/kg as part of routine immunoprophylaxis) within 3 wk of exposure.

Dosing Interactions Contraindications Precautions

Adult

15 mL IM; divide dose into several muscle sites to reduce local pain
Pediatric

0.25 mL/kg IM (0.5 mL/kg for patients with HIV); not to exceed a cumulative dose of 15 mL; if dose exceeds 10 mL, divide dose into several muscle sites to reduce local pain

Follow-up
Further Inpatient Care

Hospitalization may be indicated for treatment of measles complications (eg, bacterial superinfection, pneumonia, dehydration, croup).

Inpatient & Outpatient Medications

Perform timely contact tracing and institute prophylaxis or immunization, if indicated

Deterrence/Prevention

The Measles Initiative is a collaborative effort of the WHO, the United Nations Children's Fund (UNICEF), the American Red Cross, the CDC, and the United Nations Foundation, along with other public and private partners. The WHO and UNICEF are collaborating to reduce global measles death by 90% by the year 2010. The goals of the program include the following:
o o

Routine immunization for children by their first birthday A second opportunity for measles immunization through mass vaccination campaigns to ensure that all children receive at least one dose

Effective surveillance in all countries to quickly recognize and respond to measles outbreaks Enhanced treatment of measles, including vitamin A supplements and supportive care and antibiotics if needed to prevents complications

Prevention requires vaccination with live-attenuated measles vaccine (per routine) or earlier immunization (ie, no <6 mo) during epidemics. Human immunoglobulin (Ig) prevents or modifies disease in susceptible contacts if administered within 6 days of exposure.

Complications

Common infectious complications include otitis media, interstitial pneumonitis, bronchopneumonia, laryngotracheobronchitis (ie, croup), exacerbation of tuberculosis, transient loss of hypersensitivity reaction to tuberculin skin test, encephalomyelitis, and diarrhea. Rare complications include hemorrhagic measles, purpura fulminans, hepatitis, disseminated intravascular coagulation (DIC), and subacute sclerosing panencephalitis (SSPE). Transient hepatitis may occur during an acute infection. Approximately 1 of every 1,000 patients develops acute encephalitis, which often results in permanent brain damage. SSPE, a degenerative CNS disease, can result from a persistent measles infection. SSPE is characterized by the onset of behavioral and intellectual deterioration and seizures years after an acute infection (the mean incubation period for SSPE is approximately 10.8 y).

Prognosis

Most children recover uneventfully. High case-fatality rates may be observed among children who are malnourished or immunodeficient, particularly in developing nations. Overall, case-fatality rate in the United States has been less than 0.1%.

Patient Education

For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections. Also, see eMedicine's patient education articles Measles and Skin Rashes in Children.

Miscellaneous
Medicolegal Pitfalls

Failure to diagnose measles or its complications

Special Concerns

Because the transmission of indigenous measles has been interrupted in the United States and all recent US epidemics have been linked to imported cases, immediately

reporting any suspected case of measles to a local or state health department is imperative, as is obtaining serum for IgM antibody testing as soon as possible (ie, on or after the third day of rash). Airborne precautions are indicated for hospitalized children during the period of communicability (ie, 3-5 d before appearance of rash to 4 d after the rash develops in healthy children and for the duration of illness in patients who are immunocompromised). Susceptible health care workers should be excused from work from the fifth to the 21st day after exposure. A syndrome called atypical measles has been described in individuals who were infected with wild measles virus (MV) several years after immunization with a killed measles vaccine (a vaccine used in the United States from 1963-1967). The disease tends to be more prolonged and severe than regular measles and is marked by a prolonged high fever, pneumonitis, and a rash that begins peripherally and may be urticarial, maculopapular, hemorrhagic, and/or vesicular. The assumed pathogenesis is hypersensitivity to MV in a partially immune host. 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 IgG antibody titer (eg, 1:1,000,000) in the serum.