Kliegman: Nelson Textbook of Pediatrics, 18th ed.

Copyright 2007 Saunders, An Imprint of Elsevier Chapter 243 Measles Wilbert H. Mason Measles is highly contagious and was once an inevitable experience during childhood. Due to widespread vaccination, endemic transmission has been interrupted in the United States; however, indigenous or imported cases have occasionally resulted in epidemics in the United States. In some areas of the world, measles remains a serious threat to children.
ETIOLOGY.

Measles virus is a single-stranded lipid enveloped RNA virus in the family Paramyxoviridae and genus Morbillivirus. Other members of this genus are rinderpest virus of cattle and distemper virus of dogs, but humans are the only host of measles virus. Of the 6 major structural proteins of measles virus, the 2 most important in terms of induction of immunity are the hemagglutinin (H) protein and the fusion (F) protein. The neutralizing antibodies are directed against the H protein, and antibodies to the F protein limit proliferation of the virus during infection. Small variations in genetic composition have also been identified that result in no effect on protective immunity but provide molecular markers that can distinguish between viral types. These markers have been useful in the evaluation of endemic spread of measles.
EPIDEMIOLOGY.

The measles vaccine has changed the epidemiology of measles dramatically. Once worldwide in distribution, endemic transmission of measles has been interrupted in many countries where there is widespread vaccine coverage. Historically, in the United States it caused universal infection in childhood with 90% of children acquiring the infection before 15 yr of age. Morbidity and mortality associated with measles decreased prior to the introduction of the vaccine due to improved health care and nutrition. However, the incidence declined dramatically following the introduction of the measles vaccine 1963. The attack rate fell from 313 cases/100,000 population in 195660 to 1.3 cases/100,000 in 198288. It is most common in the winter and spring. A nationwide indigenous measles outbreak occurred in 19891991 resulting in >55,000 cases, 11,000 hospitalizations, and 123 deaths, demonstrating that the infection had not yet been conquered. The resurgence was attributed to vaccine failure in a small number of school-aged children and low coverage of preschool-aged children and because of more rapid waning of maternal antibodies in infants born to mothers who never experienced wild-type measles infection. Implementation of the 2 dose vaccine policy and more intensive immunization strategies resulted in interruption of endemic transmission in the United States in 1993. The current rate is <1 case/1,000,000 population.

Measles continues to be imported into the United States from abroad; therefore, continued maintenance of >90% immunity through vaccination is necessary to prevent widespread outbreaks from occurring ( Fig. 243-1 ).

Figure 243-1 Incidence* and percentage of import-associated measles cases, by year in the United States, 19852003. (From the Centers for Disease Control and Prevention: Epidemiology of measlesUnited States, 20012003. MMWR 2004;53:713716.)

TRANSMISSION.

The portal of entry of measles virus is through the respiratory tract or conjunctivae following contact with large droplets or small droplet aerosols in which the virus is suspended. Patients are infectious from 3 days before the rash up to 46 days after its onset. Approximately 90% of the exposed susceptible individuals develop measles. Face-to-face contact is not necessary because viable virus may be suspended in air up to 1 hr after a source case leaves a room. Secondary cases have been reported in physicians' offices and in hospitals by spread of aerosolized virus.
PATHOLOGY.

Measles infection causes necrosis of the respiratory tract epithelium and an accompanying lymphocytic infiltrate. Measles produces a small vessel vasculitis on the skin and on the oral mucous membranes. Histology of the rash and exanthem reveals intracellular edema and dyskeratosis associated with formation of epidermal syncytial giant cells with up to 26 nuclei. Viral particles have been identified within these giant cells. In lymphoreticular tissue, lymphoid hyperplasia is prominent. Fusion of infected cells results in multinucleated giant cells, theWarthin-Finkeldey giant cells that are pathognomonic for measles, with up to 100 nuclei and intracytoplasmic and intranuclear inclusions ( Fig. 243-2 ).

Figure 243-2 Warthin-Finkeldey cell from lung tissue. (Courtesy of Robert M. McAllister, MD, Children's Hospital Los Angeles [retired].)

PATHOGENESIS.

Measles consists of 4 phases: incubation period, prodromal illness, exanthematous phase, and recovery. During incubation, measles virus migrates to regional lymph nodes. A primary viremia ensues that disseminates the virus to the reticuloendothelial system. A secondary viremia spreads virus to body surfaces. The prodromal illness begins following the secondary viremia and is associated with epithelial necrosis and giant cell formation in body tissues. Cells are killed by cell-to-cell plasma membrane fusion associated with viral replication that occurs in many body tissues, including cells of the central nervous system (CNS). Virus shedding begins in the prodromal phase. With onset of the rash, antibody production begins and viral replication and symptoms begin to subside. Measles virus also infects CD4+ T cells, resulting in suppression of the Th1 immune response and a multitude of other immunosuppressive effects.
CLINICAL MANIFESTATIONS.

Measles is a serious infection characterized by high fever, an enanthem, cough, coryza, conjunctivitis, and a prominent exanthem. After an incubation period of 812 days, the prodromal phase begins with a mild fever followed by the onset of conjunctivitis with photophobia, coryza, a prominent cough and increasing fever. The enanthem, Koplik spots, is the pathognomonic sign of measles and appears 1 to 4 days prior to the onset of the rash ( Fig. 243-3 ). They first appear as discrete red lesions with bluish white spots in the center on the inner aspects of the cheeks at the level of the premolars. They may spread to involve the lips, hard palate, and gingiva. They also may occur in conjunctival folds and in the vaginal

mucosa. Koplik spots have been reported in 5070% of measles cases but probably occur in the great majority.

Figure 243-3 Koplik spots on the buccal mucosa during the 3rd day of rash. (From the Centers for Disease Control and Prevention websitePublic Health Image Library. Image #4500. Available at http://phil.cdc.gov/phil/details.asp )

Symptoms increase in intensity for 24 days until the 1st day of the rash. The rash begins around the forehead (around the hairline), behind the ears, and on the upper neck as a red maculopapular eruption. It then spreads downward to the torso and extremities, reaching the palms and soles in up to 50% of cases. The exanthem frequently becomes confluent on the face and upper trunk (Figs. 243-4 and 243-5 [4] [5]).

Figure 243-4 A child with measles displaying the characteristic red blotchy pattern on his body during the 3rd day of the rash. (From the Centers for Disease Control and Prevention websitePublic Health Image Library. Image #4498. Available at http://phil.cdc.gov/phil/details.asp )

Figure 243-5 Close-up of the maculopapular rash of measles. (From Korting GW: Hautkrankheiten bei Kindern und Jugendlichen, 3rd ed. Stuttgart, FK Schattauer Verlag, 1982.)

With the onset of the rash, symptoms begin to subside and the rash fades over about 7 days in the same progression as it evolved, often leaving a fine desquamation of skin in its wake. Of the major symptoms of measles, the cough lasts the longest, often up to 10 days. In more severe cases, generalized lymphadenopathy may be present, with cervical and occipital lymph nodes especially prominent.
INAPPARENT MEASLES INFECTION.

In individuals with passively acquired antibody, such as infants or recipients of blood products, a subclinical form of measles may occur. The rash may be indistinct, brief, or, rarely, entirely absent. Likewise, some individuals who have received vaccine when exposed to measles may develop a rash but few other symptoms. Persons with inapparent or subclinical measles do not shed measles virus and do not transmit infection to household contacts. Children who had received the original formalin-inactivated measles vaccine at times developed a more severe form of disease called atypical measles. Patients had onset of high fever and headache followed by the appearance of a maculopapular rash on the extremities that become petechial and purpuric and progressed in a centripetal direction. The illness was frequently complicated by pneumonia and pleural effusions. It is thought that atypical measles

was caused by development of circulating immune complexes that formed due to an abnormal immune response to the vaccine.
LABORATORY FINDINGS.

The diagnosis of measles is almost always based on clinical and epidemiologic findings. Laboratory findings in the acute phase include reduction in the total white blood cell count, with lymphocytes decreased more than neutrophils. Absolute neutropenia has been known to occur, however. In measles not complicated by bacterial infection, the erythrocyte sedimentation rate and C-reactive protein levels are normal.
DIAGNOSIS.

In the absence of a recognized measles outbreak, confirmation of the clinical diagnosis is often recommended. Serologic confirmation is most conveniently made by identification of immunoglobulin M (IgM) antibody in serum. IgM antibody appears 12 days after the onset of the rash and remains detectable for about 1 mo. If a serum specimen is collected <72 hours following onset of rash and is negative for measles antibody, a repeat specimen should be obtained. Serologic confirmation may also be made by demonstration of a 4-fold rise in IgG antibodies in acute and convalescent specimens taken 24 wk later. Viral isolation from blood, urine, or respiratory secretions can be accomplished by culture at the Centers for Disease Control and Prevention (CDC) or local or state laboratories. Molecular detection by polymerase chain reaction is possible but is a research tool.
DIFFERENTIAL DIAGNOSIS.

Typical measles is unlikely to be confused with other illnesses, especially if Koplik spots are observed. Measles in the later stages or inapparent or subclinical cases may be confused with a number of other exanthematous immune-mediated illnesses and infections, including rubella, adenoviruses, enteroviruses, and Epstein-Barr virus. Exanthem subitum (in infants) and erythema infectiosum (in older children) may also be confused with measles. Mycoplasma pneumoniae and group A streptococcus may also produce rashes similar to measles. Kawasaki syndrome can manifest many of the same findings as measles but lacks discrete intraoral lesions (Koplik spots) and a severe prodromal cough, and typically has elevated neutrophils and acute-phase reactant levels. In addition, the characteristic thrombocytosis of Kawasaki syndrome is absent in measles (see Chapter 165 ). Drug eruptions may occasionally be mistaken for measles.
COMPLICATIONS.

Complications of measles are largely attributable to the pathogenic effects of the virus on the respiratory tract and immune system ( Table 243-1 ). There are several factors that make complications more likely. Morbidity and mortality from measles are greatest in patients <5 yr of age (especially <1 yr of age) and those >20 yr of age. In developing countries, higher case-fatality rates have been associated with crowding, which is possibly attributable to a larger inoculum dose following household exposure. Severe malnutrition in children results in suboptimal immune response and higher morbidity and mortality with measles infection. Low serum retinol levels in children with measles have been shown to be associated with higher measles morbidity and mortality in developing countries and in the United States. Measles infection lowers serum retinol, so subclinical cases of hyporetinolemia may be made symptomatic during measles. Measles infection in immunocompromised persons is associated

with increased morbidity and mortality. Pneumonitis occurs in 58% of patients with malignancy infected with measles, and encephalitis occurs in 20%.

TABLE 243-1 -- Complications by Age for Reported Measles Cases, USA 19872000 NO.(%) OF PERSONS WITH COMPLICATION BY AGE GROUP COMPLICATION OVERALL (67,032 CASES WITH AGE INFORMATION) Any Death Diarrhea Encephalitis Hospitalization Otitis media Pneumonia 19,480 (29.1) 177 (0.3) 5,482 (8.2) 97 (0.1) 12,876 (19.2) 4,879 (7.3) 3,959 (5.9) <5 yr (n 59 yr 1019 yr 2029 >30 yr = (n = (n = yr (n = (n = 28,730) 6,492) 18,580) 9,161) 4,069) 11,883 (41.4) 1,173 (18.1) 2,369 (12.8) 2,656 (29.0) 1,399 (34.4)

97 (0.3) 9 (0.1) 18 (0.1) 3,294 (11.5) 408 (6.3)

26 (0.3) 27 (0.7) 386 (9.5)

627 (3.4) 767 (8.4)

43 (0.2) 9 (0.1) 13 (0.1) 7,470 (26.0) 4,009 (14.0) 612 (9.4) 305 (4.7) 1,612 (8.7)

21 (0.2) 11 (0.3) 2,075 (22.7) 1,107 (27.2) 70 (1.7)

338 (1.8) 157 (1.7)

2,480 183 363 (2.0) 554 379 (8.6) (2.8) (6.1) (9.3) From Perry RT, Halsey NA:The clinical significance of measles:A review. Clin Infect Dis 2004;189(Suppl 1):S4S16.

Pneumonia is the most common cause of death in measles. It may manifest as giant cell pneumonia caused directly by the viral infection or as superimposed bacterial infection. The most common bacterial pathogens are S. pneumoniae, H. influenzae, and S. aureus. Following severe measles pneumonia, the final common pathway to a fatal outcome is often the development of bronchiolitis obliterans. Croup, tracheitis, and bronchiolitis are common complications in infants and toddlers with measles. The clinical severity of these complications frequently requires intubation and ventilatory support until the infection resolves. Acute otitis media is the most common complication of measles and was of particularly high incidence during the epidemic of the late 1980s and early 1990s because of the relatively young age of affected children. Sinusitis and mastoiditis also occur as complications. Viral and/or bacterial tracheitis are seen and can be life threatening. Retropharyngeal abscess has also been reported.

Measles infection is known to suppress skin test responsiveness to purified tuberculin antigen. There may be an increased rate of activation of pulmonary tuberculoses in populations of individuals infected with Mycobacterium tuberculosis. Diarrhea and vomiting are common symptoms associated with acute measles, and the gastrointestinal tract has diffuse giant cell formation in the epithelium. Dehydration is a common consequence, especially in young infants and children. Appendicitis may occur due to obstruction of the appendiceal lumen by lymphoid hyperplasia. Febrile seizures occur in <3% of children with measles. Encephalitis following measles has been a long-associated complication, often with an unfavorable outcome. Rates of 13/1,000 cases of measles have been reported, with greater numbers occurring in adolescents and adults than in preschool or school-aged children. This is a postinfectious immunologically mediated process rather than due to a direct effect by the virus. Clinical onset begins during the exanthem and presents with seizures (56%), lethargy (46%), coma (28%), and irritability (26%). Findings in cerebrospinal fluid include lymphocytic pleocyosis in 85% and elevated protein concentration. Approximately 15% of patients die, and 2040% suffer long-term sequelae, including mental retardation, motor disabilities, and deafness. Measles encephalitis in immunocompromised patients results from direct damage to the brain by the virus. Subacute measles encephalitis presents 110 mo following measles in immunocompromised patients, particularly those with AIDS, lymphoreticular malignancies, and immunosuppression. Signs and symptoms include seizures, myoclonus, stupor, and coma. In addition to intracellular inclusions, abundant viral nucleocapsids and viral antigen are seen in brain tissue. Progressive disease and death almost always occurs. A severe form of measles rarely seen now is hemorrhagic or black measles. It presented with a hemorrhagic skin eruption and was often fatal. Keratitis, appearing as multiple punctate epithelial foci, resolved with recovery from the infection. Thrombocytopenia sometimes occurred following measles. Myocarditis is a rare complication. Miscellaneous bacterial infections have been reported, including bacteremia, cellulitis, and toxic shock syndrome. Measles during pregnancy has been associated with high maternal morbidity, fetal wastage and stillbirths, and congenital malformations in 3% of live born infants.
Subacute Sclerosing Parencephalitis (SSPE).

SSPE is a chronic complication of measles with a delayed onset and an outcome that is nearly always fatal. It appears to result from a persistent infection with an altered measles virus that is harbored intracellularly in the CNS for several years. After 710 yr the virus apparently regains virulence and attacks the cells in the CNS that offered the virus protection. This slow virus infection results in inflammation and cell death, leading to an inexorable neurodegenerative process. SSPE is a rare disease and generally follows the prevalence of measles in a population. The incidence rate in the USA in 1960 was 0.61 cases per million persons younger than 20 yr. By 1980 the rate had fallen to 0.06 cases per million. Between 1956 and 1982 a total of 634 cases had been reported to the national SSPE registry. After 1982 about 5 cases per year were reported annually in the United States and only 23 cases per year in the early 1990s.

However, between 1995 and 2000, reported cases in the USA increased and 13 cases were reported in 2000. Nine of the 13 cases occurred in foreign-born individuals. This resurgence may be the result of an increased incidence of measles between 1989 and 1991. While the age of onset ranges from <1 to <30 yr, the illness is primarily one of children and adolescents. Measles at an early age favors the development of SSPE: 50% of SSPE patients had primary measles before 2 yr and 75% before 4 yr of age. Males are affected twice as often as females, and there appear to be more cases reported from rural rather than urban populations. Recent observations from the registry indicate a higher prevalence among children of Hispanic origin. The pathogenesis of SSPE remains enigmatic. Factors that seem to be involved include defective measles virus and interaction with a defective or immature immune system. The virus isolated from brain tissue of patients with SSPE is missing 1 of the 6 structural proteins, the matrix or M protein. This protein is responsible for assembly, orientation, and alignment of the virus in preparation for budding during viral replication. Immature virus may be able to reside, and possibly propagate, within neuronal cells for long periods. The fact that most patients with SSPE were exposed at a young age suggests that immune immaturity is involved in pathogenesis. In addition, the intracellular location of the virus sequesters it from the immune system, especially from humoral immunity. Clinical manifestations of SSPE begin insidiously 713 yr after primary measles infection. Subtle changes in behavior or school performance appear, including irritability, reduced attention span, or temper outbursts. This initial phase (stage I) may at times be missed because of brevity or mildness of the symptoms. Fever, headache, or other signs of encephalitis are absent. The hallmark of the 2nd stage is massive myoclonus. This coincides with extension of the inflammatory process site to deeper structures in the brain, including the basal ganglia. Involuntary movements and repetitive myoclonic jerks begin in single muscle groups but give way to massive spasms and jerks involving both axial and appendicular muscles. Consciousness is maintained. In the 3rd stage, involuntary movements disappear and are replaced by choreoathetosis, immobility, dystonia, and lead pipe rigidity that result from destruction of deeper centers in the basal ganglia. Sensorium deteriorates into dementia, stupor, then coma. Stage IV is characterized by loss of critical centers that support breathing, heart rate, and blood pressure. Death soon ensues. Progression through the clinical stages may follow courses characterized as acute, subacute, or chronic progressive. The diagnosis of SSPE can be established through documentation of a compatible clinical course and at least 1 of the following supporting findings: (1) measles antibody detected in CSF, (2) characteristic electroencephalographic findings, or (3) typical histologic findings and/or isolation of virus or viral antigen in brain tissue obtained by biopsy or postmortem examination. CSF analysis reveals normal cells but elevated IgG and IgM antibody titers in dilutions of >1 : 8. Electroencephalographic patterns are normal in stage I, but in the myoclonic phase suppression-burst episodes are seen that are characteristic of but not pathogenomic for SSPE. Brain biopsy is no longer routinely indicated for diagnosis of SSPE. Management of SSPE is primarily supportive and similar to care provided to patients with other neurodegenerative diseases. A recent large randomized clinical trial compared the use of oral inosiplex (isoprinosine) alone to oral inosiplex and intraventricular interferon-2b. The treatment course for both groups was 6 mo. While there were no differences in the rates of stabilization or improvement at 6 mo (34% vs 35%), the study concluded that these rates were substantially better than historically reported spontaneous improvement rates of 510%.

Virtually all patients eventually succumb to SSPE. Most die within 13 yr of onset from infection or loss of autonomic control mechanisms. Prevention of SSPE depends on prevention of primary measles infection through the use of vaccine. SSPE has been described in patients who have no history of measles infection and only exposure to the vaccine virus. However wild-type virus, not vaccine virus, has been found in brain tissue of at least some of these patients, suggesting they had had subclinical measles previously.
TREATMENT.

Management of measles is supportive. Antiviral therapy is not effective in the treatment of measles in otherwise normal patients. Maintenance of hydration, oxygenation, and comfort are goals of therapy. Antipyretics for comfort and fever control are useful. For patients with respiratory tract involvement, airway humidification and supplemental oxygen may be of benefit. Respiratory failure due to croup or pneumonia may require ventilatory support. Oral rehydration is effective in most cases, but severe dehydration may require intravenous therapy. Prophylactic antimicrobial therapy to prevent bacterial infection is not indicated. Measles infection in immunocompromised patients is highly lethal. Ribavirin is active in vitro against measles virus. Anecdotal reports of ribavirin therapy with or without intravenous gamma globulin suggest some benefit in individual patients. However, no controlled trials have been performed, and ribavirin is not licensed in the United States for treatment of measles.
VITAMIN A.

Vitamin A deficiency in children in developing countries has long been known to be associated with increased mortality from a variety of infectious diseases, including measles. In the United States, studies in the early 1990s documented that 2272% of children with measles had low retinol levels. In addition, 1 study demonstrated an inverse correlation between the level of retinol and severity of illness. Several randomized controlled trials of vitamin A therapy in the developing world and the United States have demonstrated reduced morbidity and mortality from measles. The American Academy of Pediatrics suggests vitamin A therapy for selected patients with measles ( Table 243-2 ).

TABLE 243-2 -- Recommendations for Vitamin A Treatment of Children with Measles INDICATIONS Children 6 mo to 2 yr of age hospitalized with measles and its complications (e.g., croup, pneumonia, and diarrhea). (Limited data are available about the safety and need for vitamin a supplementation for infants <6 mo of age.) Children >6 mo of age with measles who are not already receiving vitamin A supplementation and who have any of the following risk factors: immunodeficiency clinical evidence of vitamin A deficiency impaired intestinal absorption moderate to severe malnutrition

recent immigration from areas where high mortality rates attributed to measles have been observed

REGIMEN Parenteral and oral formulations of vitamin A are available in the USA. The recommended dosage, administered as a capsule, is: Single dose of 200,000 IU orally for children 1 yr of age (100,000 IU for children 6 mo to 1 yr of age) The dose should be repeated the next day and again 4 wk later for children with ophthalmologic evidence of vitamin A deficiency

From the American Academy of Pediatrics, Committee on Infectious Disease: Vitamin A treatment of measles. Pediatrics
PROGNOSIS.

In the early 20th century, deaths due to measles varied between 2,000 and 10,000, or about 10 deaths per 1,000 cases of measles. With improvements in health care and antimi crobial therapy, better nutrition, and decreased crowding, the death to case ratio fell to 1 per 1,000 cases. Between 1982 and 2002, the CDC estimated there were 259 deaths caused by measles in the United States, with a death-to-case ratio of 2.52.8/1,000 cases of measles. Pneumonia and encephalitis were complications in most of the fatal cases, and immunodeficiency conditions were identified in 1416% of deaths.
PREVENTION.

Patients shed measles virus from 7 days after exposure to 46 days after the onset of rash. Exposure of susceptible individuals to measles patients should be avoided during this period. In hospitals, standard and airborne precautions should be observed for this period. Immunocompromised patients with measles will shed for the duration of the illness, and isolation should be maintained throughout.
VACCINE.

Measles vaccine in the United States is available as a monovalent preparation or combined with the rubella (MR) or measles-mumps-rubella (MMR) vaccine, which is the recommended form in most circumstances ( Table 243-3 ). Following the measles resurgence of 19891991, a 2nd dose of measles vaccine was added to the schedule. The current recommendations include a 1st dose at 1215 mo followed by a 2nd at 46 yr of age. Seroconversion is slightly lower in children who receive the 1st dose before or at 12 mo of age (87% at 9 mo, 95% at 12 mo, and 98% at 15 mo) because of persisting maternal antibody. For children who have not received 2 doses by 1112 yr of age, a 2nd dose should be provided. Infants who receive a dose before 12 mo of age should be given 2 additional doses at 1215 mo and 46 yr of age. In any event, this 2nd dose of vaccine may be given anytime 4 wk after the 1st dose. TABLE 243-3 -- Recommendations for Measles Immunization[*] CATEGORY RECOMMENDATIONS

CATEGORY

RECOMMENDATIONS

Unimmunized, no history of measles A 2 dose schedule (with MMR) is recommended. (1215 mo of age) The first dose is recommended at 1215 mo of age; the 2nd is recommended at 46 yr of age Children 611 mo of age in epidemic situations or prior to international travel Children 412 yr of age who have received 1 dose of measles vaccine at 12 mo of age Students in college and other post high school institutions who have received 1 dose of measles vaccine at 12 mo of age History of immunization before the 1st birthday Immunize (with monovalent measles vaccine, or if not available, MMR);reimmunization (with MMR) at 12 15 mo of age is necessary, and a 3rd dose is indicated at 46 y of age Reimmunize (1 dose)

Reimmunize (1 dose)

Consider susceptible and immunize (2 doses)

History of receipt of inactivated Consider susceptible and immunize (2 doses) measles vaccine or unknown type of vaccine, 19631967 Further attenuated or unknown vaccine given with IG Allergy to eggs Neomycin allergy, nonanaphylactic Consider susceptible and immunize (2 doses) Immunize;no reactions likely (see text for details) Immunize;no reactions likely (see text for details)

Severe hypersensitivity Avoid immunization (anaphylaxis) to neomycin or gelatin Tuberculosis Immunize (see Tuberculosis);if patient has untreated tuberculosis disease, start anti-tuberculosis therapy before immunizing. Immunize and/or give IG, depending on circumstances (see text) Immunize (2 doses) unless severely immunocompromised (see text) Immunize;advise parents of slightly increased risk of seizures

Measles exposure HIV-infected Personal or family history of seizures

Immunoglobulin or blood recipient Immunize at the appropriate interval (see Table 243-4) American Academy of Pediatrics: Red Book:2006 Report of the Committee on Infectious Diseases, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, p 446.
* IG, immune globulin;MMR, measles-mumps-rubella vaccine. See text for details and recommendations for use of measles-

mumps-rubella-varicella (MMRV) vaccine.

Adverse events from the MMR vaccine include fever (usually 612 days following vaccinations), rash in about 5% of vaccines, and, rarely, transient thrombocytopenia. Children prone to febrile seizures may experience an event following vaccination, so risks and benefits should be discussed with parents. Encephalopathy and autism have not been shown to be causally associated with the MMR vaccine. Specifically, MMR vaccine significantly diminishes the risk for SSPE. Passively acquired, immunoglobulin may inhibit the immune response to live measles vaccine, and administration should be delayed for variable amounts of time based on the dose of immune globulin ( Table 243-4 ).

TABLE 243-4 -- Suggested Intervals Between Immune Globulin Administration and Measles Immunization (MMR, MMRV, or Monovalent Measles Vaccine) INDICATION FOR INTERVAL, IMMUNOGLOBULIN DOSE MO[*] ROUTE U or mL Tetanus (as TIG) Hepatitis A prophylaxis (as IG) Contact prophylaxis International travel Hepatitis B prophylaxis (as HBIG) Rabies prophylaxis (as RIG) Varicella prophylaxis (as VariZIG) Measles prophylaxis (as IG) Standard Immunocompromised host RSV prophylaxis (palivizumab monoclonal antibody) Cytomegalovirus immune globulin Blood transfusion Washed RBCs RBCs, adenine-saline added Packed RBCs Whole blood Plasma or platelet products Replacement (or therapy) of IV IV IV IV IV IV 10 mL/kg 10 mL/kg 10 mL/kg 10 mL/kg 10 mL/kg Negligible 10 2060 80100 160 300400 0 3 5 6 7 8 IM IM IM IV 0.25 mL/kg 0.50 mL/kg 3 mL/kg 40 80 15 mg/kg (monoclonal) 150 5 6 None 6 IM IM IM IM IM 0.02 mL/kg 0.06 mL/kg 0.06 mL/kg 20 IU/kg 125 U/10 kg (maximum 625 U) 3.3 10 10 22 2040 3 3 3 4 5 IM 250 U mg lgG/kg 10 3

INDICATION FOR IMMUNOGLOBULIN immune deficiencies (as IGIV) ITP (as IGIV) ITP IV IV

DOSE ROUTE U or mL mg lgG/kg 400 1,000

INTERVAL, MO[*]

8 10

ITP or Kawasaki disease IV 1,6002,000 11 American Academy of Pediatrics: Red Book:2006 Report of the Committee on Infectious Disease, 27th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2006, p 445. * HBIG, hepatitis B IG;IG, immune globulin;IgG, immunoglobulin G; IGIV, IG intravenous;ITP, immune (formerly termed idiopathic) thrombocytopenic purpura; MMR, measles-mumps-rubella; MMRV, measles-mumps-rubella-varicella; RBCs, red blood cells;RIG, rabies IG;RSV, respiratory syncytial virus;TIG, tetanus immune globulin.
* These intervals should provide sufficient time for decreases in passive antibodies in all children to follow for an adequate

response to measles vaccine. Physicians should not assume that children are fully protected against measles during these intervals. Additional doses of IG or measles vaccine may be indicated after exposure to measles (see text).

Live vaccines should not be administered to pregnant women or immunodeficient or suppressed patients. However, patients with HIV who are not severely immunocompromised should be immunized. Because measles virus may suppress the cutaneous response to tuberculous antigen, skin testing for tuberculosis should be performed before or at the same time as administration of the vaccine. Individuals infected with M. tuberculosis should be on appropriate treatment at the time of administration of measles vaccine.
POSTEXPOSURE PROPHYLAXIS.

Susceptible individuals exposed to measles may be protected from infection either by vaccine administration or immunization with immunoglobulin. The vaccine is effective in prevention or modification of measles if given within 72 hr of exposure. Immune globulin may be given up to 6 days following exposure to prevent or modify infection. Immunocompetent children should receive 0.25 mL/kg intramuscularly and immunocompromised children should receive 0.5 mL/kg. Immune globulin is indicated for susceptible household contacts of measles patients, especially infants <6 mo of age, pregnant women, and immunocompromised persons. Email to Colleague Print Version Copyright 2008 Elsevier Inc. All rights reserved. - www.mdconsult.com