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Harrison’s Manual of Medicine



Measles (Rubeola)
Rubella (German Measles)
Measles is a highly contagious acute respiratory disease with a characteristic clinical picture and a pathognomonic enanthem. Measles virus is a member of the family Paramyxoviridae.
EPIDEMIOLOGY   Measles has a worldwide distribution. The disease is transmitted by respiratory secretions, predominantly via exposure to aerosols but also through direct contact with larger droplets. It is highly contagious: an infected individual can transmit the virus during a period from 1–2 d before onset of symptoms to 4 d after the appearance of skin lesions. In the U.S., the number of cases decreased progressively after the advent of routine childhood vaccination, except for a brief upsurge in 1990. By the mid-1990s, the disease was once more brought under control, with only 508 cases reported to the CDC in 1996. Most cases have since resulted from international importations of the virus. Outbreaks have involved not only unvaccinated infants and preschool children but also high school and college students with vaccination rates of >95%.
CLINICAL MANIFESTATIONS   The incubation period for measles is 8–12 d. Pts first experience 3–4 d of prodromal symptoms, including malaise, irritability, fever, conjunctivitis with excessive lacrimation, edema of the eyelids, photophobia, hacking cough, and nasal discharge. Koplik’s spots, which are pathognomonic for measles, appear 1–2 d before the onset of rash and are small, red, irregular lesions with blue-white centers found on mucous membranes, especially opposite the second molars. The rash of measles appears first on the forehead and spreads downward over the face, neck, trunk, and feet. The lesions are erythematous maculopapules that coalesce over the face and upper trunk. Most other symptoms resolve within 1–2 d of the appearance of rash, but cough may persist.
Measles is usually a self-limited disease, but a number of complications may ensue. Important complications include croup, bronchitis, and bronchiolitis; rare instances of interstitial giant cell pneumonia in immunocompromised children; conjunctivitis with progression to corneal ulceration, keratitis, and blindness; myocarditis; hepatitis; transient acute glomerulonephritis; bacterial pneumonia; and encephalomyelitis. This last complication, with headache, high fever, drowsiness, and coma, occurs in 1 of every 1000 pts within days after the appearance of rash; the mortality rate is 10%. An extremely rare condition, subacute sclerosing panencephalitis, is a late complication of measles.
Atypical measles can develop in pts who have received formalin-inactivated measles vaccine (used in the U.S. in 1963–1967) and can present with a variety of rashes; pneumonia and high fever are common. Despite the severity of atypical measles, pts invariably recover after a convalescence that may be prolonged.
DIAGNOSIS   Lymphopenia and neutropenia are common in measles; leukocytosis may herald a bacterial superinfection. Measles virus can be isolated by inoculation of sputum, nasal secretions, or urine onto cell cultures. Immunofluorescent antibody staining of infected respiratory or urinary epithelial cells can detect measles antigen. Serologic tests include complement fixation, enzyme immunoassay, immunofluorescence, and hemagglutination inhibition assays. Specific IgM antibodies are detectable within 1–2 d after the appearance of a rash, and IgG titers rise significantly after 10 d.

No therapy is indicated for uncomplicated measles. Clinical trials suggest benefit from high doses of vitamin A in severe or potentially severe measles, especially in children <2 years; a dose of 200,000 IU is used for children >1 year. Ribavirin is effective against measles virus in vitro and may be considered for use in immunocompromised individuals.

PREVENTION   Measles should be controlled by vaccination. Live attenuated measles vaccine is given to children as part of the measles-mumps-rubella (MMR) vaccine at 12–15 months and again at either 4–5 years (CDC) or 12 years (American Academy of Pediatrics). Vaccine can also be given as prophylaxis within 3 d of exposure. Pts who received killed measles vaccine between 1963 and 1967 should be considered unprotected and are at risk for atypical measles. Pts infected with HIV who are susceptible should be vaccinated against measles; actively immunosuppressed pts (including AIDS pts with <15% CD4 lymphocytes) should not receive live vaccine. Gamma globulin (0.25 mL/kg, not to exceed 15 mL) modifies or prevents acquisition of measles if given within 6 d of exposure.
Rubella is an acute viral infection that characteristically includes rash, fever, and lymphadenopathy and has a broad spectrum of other possible manifestations. Rubella virus, a togavirus, is closely related to the alphaviruses. Transmission takes place via direct or droplet contact with nasopharyngeal secretions.
CLINICAL MANIFESTATIONS   The time from exposure to appearance of the rash is 12–23 d. In adults, a prodrome of malaise, headache, fever, and anorexia may precede the rash by 1–7 d. Subclinical infection is common. The distribution of the rash in rubella is the same as that in measles, but lesions are lighter in hue in rubella and are usually discrete. The rash may be accompanied by mild coryza and conjunctivitis. Enlarged, tender lymph nodes become apparent before onset of the rash and are most impressive during the eruptive phase; postauricular and suboccipital nodes are strikingly involved. Arthralgias and slight swelling of the joints sometimes accompany rubella, especially in young women, and may persist for 1–14 d after other manifestations have disappeared. Recurrences of joint symptoms for a year or more have been reported.
The most important factor in the pathogenicity of rubella virus for the fetus is gestational age at the time of infection. Maternal infection in the first trimester is most dangerous, leading to fetal infection in about half of cases. The congenital rubella syndrome consists of heart malformations (patent ductus arteriosus, interventricular septal defect, or pulmonic stenosis), eye lesions (corneal clouding, cataracts, chorioretinitis, and microphthalmia), microcephaly, and deafness. The “expanded” rubella syndrome was defined after an American epidemic in 1964 and includes mental retardation, thrombocytopenic purpura, hepatosplenomegaly, intrauterine growth retardation, interstitial pneumonia, myocarditis or myocardial necrosis, and metaphyseal bone lesions as well as the previously described manifestations.
DIAGNOSIS   The diagnosis is made by isolation of virus, which is difficult and expensive, or by documentation of changes in antibody titers. The most commonly used test is an ELISA for IgG and IgM antibodies. Rubella antibodies may be detectable by the second day of rash and increase in titer over the next 10–21 d. Biopsied tissues and/or blood and CSF have also been used for demonstrating rubella antigens with monoclonal antibodies and for detecting rubella RNA by in situ hybridization and polymerase chain reaction.
TREATMENT AND PREVENTION   Rubella is a mild illness that does not require treatment. It is prevented by vaccination, the goal of which is the elimination of congenital infection. Live attenuated rubella vaccine is given as part of the MMR vaccine. Vaccination is contraindicated in immunosuppressed pts, but vaccine is given to children with HIV infection. Although no cases of congenital rubella syndrome have occurred in women inadvertently vaccinated during pregnancy, the vaccine should not be administered to pregnant women or to women who might become pregnant within 3 months.
Mumps is an acute, systemic, communicable viral infection whose most distinctive feature is a swelling of one or both parotid glands. The etiologic agent is a paramyxovirus.
ETIOLOGY AND EPIDEMIOLOGY   Humans are the only reservoir for mumps virus. In 1968 (before widespread immunization), 185,691 cases of mumps were reported in the U.S. The 906 cases reported in 1995 represent a reduction in the number of cases by >99% from prevaccine levels. The incubation period for mumps is generally 14–18 d. Infection tends to occur in the spring, with an especially high frequency in April and May. The virus is transmitted in infected salivary secretions but may be spread via urine as well. Infectivity is greatest from 1 or 2 d before the onset of parotitis to 5 d after the appearance of glandular enlargement; pts generally are no longer contagious 9 d after the onset of parotid swelling.
CLINICAL MANIFESTATIONS   Salivary Adenitis   There is frequently a prodrome of fever, myalgia, malaise, and anorexia. The onset of parotitis is usually sudden and in many cases is the first sign of illness. Pain and tenderness are generally marked; warmth and erythema are unusual. In two- thirds of cases, swelling is bilateral, although the onset on the two sides may not be synchronous. The submaxillary and sublingual glands are involved less often than the parotid glands and are almost never involved alone.
Epididymoorchitis   Orchitis is a complication of mumps in 20% of postpubertal males. Testicular involvement, which is bilateral in <15% of cases, usually appears 7–10 d after the onset of parotitis but may precede it or develop simultaneously. Occasionally, mumps orchitis occurs without parotitis. The testicle becomes swollen to several times its normal size and is acutely painful, with accompanying high fevers, shaking chills, malaise, and headache. In 50% of cases, orchitis is followed by atrophy; even with bilateral involvement, sterility is rare in the absence of atrophy. Oophoritis in women is far less common than orchitis in men.
Pancreatitis   Pts with pancreatic involvement develop abdominal pain and tenderness; shock and pseudocyst formation are rare. While serum amylase levels are elevated in parotitis as well as in mumps pancreatitis, serum lipase levels are increased only in the latter.
CNS Involvement   Up to 50% of pts with clinical mumps have lymphocytic pleocytosis of the CSF, with up to 1000 cells/µL; 5–25% have symptoms of meningitis (headache, stiff neck, drowsiness). CNS symptoms tend to occur 3–10 d after onset of parotitis; in 30–40% of laboratory-proven cases, parotitis is absent. True encephalitis is unusual. Mumps can produce mild paralytic poliomyelitis and, in rare cases, transverse myelitis, cerebellar ataxia, or Guillain- Barré syndrome.
Other Manifestations   Mumps virus can cause subacute thyroiditis, ocular manifestations (dacryoadenitis, optic neuritis, keratitis, iritis, conjunctivitis, and episcleritis), myocarditis, hepatitis (without jaundice), thrombocytopenic purpura, interstitial pneumonia (in young children), polyarthritis, and acute hemorrhagic glomerulonephritis.
DIAGNOSIS   Definitive diagnosis depends on isolation of the virus from saliva, throat swabs, CSF, or urine. Rapid diagnosis can be made by immunofluorescence assay for viral antigen in oropharyngeal cells. The best serologic test is the ELISA. Acute mumps can be diagnosed either by examination of acute- and convalescent-phase sera for an increase in antibody titer or by demonstration of specific IgM in one serum specimen.

No treatment is generally needed. Therapy for parotitis and other manifestations of mumps is usually symptom-based. Glucocorticoids have no proven value for the treatment of severe orchitis. Anecdotal information on a small number of pts with orchitis suggests that the administration of interferon a may be helpful.

PREVENTION   Live attenuated mumps vaccine is administered at 12– 15 months of age and again at 4–12 years as part of the MMR vaccine. Vaccination is not recommended for pregnant women, for pts receiving glucocorticoids, or for other immunocompromised hosts. However, children with HIV infection who are not severely immunocompromised can be safely immunized against mumps.
ETIOLOGY   One parvovirus, designated B19, is known to be a human pathogen. It is a small, nonenveloped, single-stranded DNA virus.
EPIDEMIOLOGY   Although B19 infections occur year-round, outbreaks of erythema infectiosum occur in schools during winter and spring months. Symptomatic infection occurs in 20–60% of children in outbreaks; 10% of infections are asymptomatic. Pts with transient aplastic crisis are highly infectious. The route of transmission of parvovirus B19 is unknown but may be respiratory or through direct contact.
CLINICAL MANIFESTATIONS   Erythema Infectiosum   Erythema infectiosum, or fifth disease, is the most common manifestation of parvovirus B19 infection and is seen predominantly in children. The typical presentation is a facial rash with a “slapped cheek” appearance, sometimes preceded by low- grade fever. The rash also develops on the arms and legs, with a lacy, reticular, erythematous appearance. Arthralgias and arthritis are uncommon in children but common in adults; rash is often absent or nonspecific in adults.
Arthropathy   Parvovirus B19 infection in adults most often involves arthralgias and arthritis, sometimes accompanied by rash. Wrists, hands, and knees are most frequently involved in symmetric, nondestructive arthritis. Symptoms usually last about 3 weeks but may persist for months (or even years) in a small percentage of cases.
Transient Aplastic Crisis   This syndrome develops in pts with chronic hemolytic disease, including sickle cell disease, erythrocyte enzyme deficiencies, hereditary spherocytosis, thalassemias, paroxysmal nocturnal hemoglobinuria, and autoimmune hemolysis. Pts develop sudden, severe anemia that can be life- threatening and can be accompanied by weakness, lethargy, and pallor. Bone marrow examination reveals an absence of erythrocyte precursors despite a normal myeloid series. Reticulocytopenia usually lasts for 7–10 d. Unlike pts with fifth disease or arthritis, these pts are viremic and infectious.
Chronic Anemia   Immunodeficient pts—e.g., those with HIV infection, congenital immunodeficiencies, or acute lymphocytic leukemia (during maintenance chemotherapy)—and recipients of bone marrow transplants may develop chronic, transfusion-dependent anemia due to parvovirus B19 infection, with destruction of erythroid precursors in the bone marrow.
Fetal Infection   Maternal infection usually does not adversely affect the fetus. Parents should be counseled as to the relatively low risk of infection to the fetus. Fewer than 10% of maternal B19 infections lead to fetal death; when fetal death occurs, the cause is nonimmune hydrops fetalis. There is no evidence that B19 infection causes congenital anomalies. Exposure of a pregnant woman to a child with fifth disease is unlikely to result in maternal infection, since the infectious stage of illness is probably over by the time the rash develops. Pregnant women with known exposure to B19 virus should have their serum monitored for IgM antibodies to the virus and for a-fetoprotein levels, and ultrasonic examinations of the fetus for hydrops should be conducted. Some hydropic fetuses survive B19 infection and appear normal at delivery.
DIAGNOSIS   Diagnosis relies on measurements of parvovirus B19–specific IgM and IgG antibodies. Pts with transient aplastic crisis may have IgM antibodies but nevertheless usually have high titers of virus and viral DNA in serum. Immunodeficient pts with chronic anemia lack antibody but have viral particles and viral DNA in serum. Viral DNA may be detected in amniotic fluid or fetal blood in cases of hydrops fetalis. Fetal infection may be recognized by hydrops fetalis and the presence of B19 DNA in amniotic fluid or fetal blood in association with maternal IgM antibodies to B19 virus.

Erythema infectiosum requires no treatment; arthritis can be treated with NSAIDs. Transient aplastic crisis is usually treated with erythrocyte transfusions. Anemia in immunodeficient pts appears to respond to treatment with commercial IV gamma globulin.

PREVENTION   Prophylaxis of B19 infection with immunoglobulin should be considered for pts with chronic hemolysis or immunodeficiency and for pregnant women. Pts hospitalized with transient aplastic crisis or chronic anemia that is suspected of being related to parvovirus B19 should be put in private rooms and managed with droplet precautions.

For a more detailed discussion, see Gershon A: Measles (Rubeola), Chap. 194, p. 1143; Rubella (German Measles), Chap. 195, p. 1145; and Mumps, Chap. 196, p. 1147; Blacklow NR: Parvovirus, Chap. 187, p. 1117, in HPIM- 15.


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