Harrisons Manual of Medicine, 18th Ed.

CHAPTER 111. Rubeola, Rubella, Mumps, and Parvovirus Infections


Definition and Microbiology

Measles is a highly contagious disease that is characterized by a prodromal illness of fever, cough, coryza, and conjunctivitis followed by a generalized maculopapular rash. Measles is caused by a nonsegmented, single-stranded, negative-sense RNA virus of the genus Morbillivirus and the family Paramyxoviridae.


Humans are the only reservoir for measles virus; unvaccinated infants who have lost maternal antibodies account for the bulk of susceptible individuals. However, as measles vaccine coverage increases, the age distribution of the disease shifts upward: in the United States, adolescents and adults are the most likely age groups to acquire measles.

• Routine administration of the measles vaccine has markedly reduced worldwide mortality due to measles; in 2008, there were ~164,000 deaths.

• Pts are contagious for several days before and after the rash appears. The virus is spread primarily via respiratory droplets over short distances. Secondary attack rates among susceptible contacts are >90%.

Clinical Manifestations

Approximately 10 days after infection with measles virus, pts develop fever and malaise, followed by cough, coryza, and conjunctivitis; the characteristic rash occurs 14 days after infection.

• An erythematous, nonpruritic, maculopapular rash begins at the hairline and behind the ears, spreads down the trunk and limbs to include the palms and soles, can become confluent, and begins to fade (in the same order of progression) by day 4.

• Koplik’s spots are pathognomonic for measles and consist of bluish-white dots ~1 mm in diameter surrounded by erythema. They appear on the buccal mucosa ~2 days before the rash appears and fade with the onset of rash.

• Pts with impaired cellular immunity may not develop a rash and have a higher case-fatality rate than those with intact immunity.

• Complications include giant-cell pneumonitis, secondary bacterial infection of the respiratory tract (e.g., otitis media, bronchopneumonia), and CNS disorders.

– Postmeasles encephalitis occurs within 2 weeks of rash onset in ~1 in 1000 cases and is characterized by fever, seizures, and a variety of neurologic abnormalities.

– Measles inclusion-body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE) occur months to years after acute infection and are caused by persistent measles virus infection.

• MIBE is a fatal complication that primarily affects pts with defects in cellular immunity.

• SSPE is a progressive disease characterized by seizures and deterioration of cognitive and motor functions, with death occurring 5–15 years after measles virus infection.


The characteristic rash and pathognomonic Koplik’s spots permit a clinical diagnosis.

• Serologic testing is the most common method of laboratory diagnosis. Measles-specific IgM is usually detectable within 1–3 days of rash onset.

• Viral culture and reverse-transcription PCR analysis of clinical specimens are used occasionally to detect measles.


• Supportive care is the mainstay of treatment, as there is no specific antiviral therapy for measles. Prompt antibiotic therapy for pts with secondary bacterial infections helps reduce morbidity and mortality risks.

• Vitamin A (for children ≥12 months: 200,000 IU daily for 2 days) is recommended by the World Health Organization (WHO) for all children with measles.


In the U.S., children are routinely immunized with two doses of a live attenuated vaccine containing measles, mumps, and rubella (MMR) antigens.

• Vaccine-induced immunity lasts for at least several decades; rates of secondary vaccine failure 10–15 years after immunization are ~5%. In contrast, natural infection leads to life-long immunity.

• Administration of immunoglobulin within 6 days of exposure, which can prevent or modify the disease in immunocompetent persons, is recommended for children <1 year old, immunocompromised pts, and pregnant women. A dose of 0.25 mL/kg is given to healthy pts and a dose of 0.5 mL/kg to immunocompromised hosts, with a maximal dose of 15 mL.


Microbiology and Epidemiology

Rubella is a contagious infectious disease caused by a single-stranded, enveloped RNA virus in the family Togaviridae and the genus Rubivirus.

• In 2007, there were ~165,000 cases of rubella worldwide, although this figure is probably an underestimate because of poor reporting. Since 2004, rubella has not been an endemic disease in the U.S.

• Virus is spread via respiratory droplets, and primary implantation and replication occur in the nasopharynx. Placental infection can lead to chronic infection of virtually all fetal organs, which sometimes persists for up to 1 year after birth.

Clinical Manifestations

While acquired rubella infection is generally benign, congenital rubella infection can be more severe.

• Acquired infection: With an incubation period of 14 days, acquired rubella is characterized by a generalized maculopapular rash that lasts for ≤3 days; ~50% of infections are subclinical.

– Occipital and/or postauricular lymphadenopathy may occur during the second week after exposure.

– In older children and adults, the rash may be preceded by a 1- to 5-day prodrome consisting of low-grade fever, malaise, and upper respiratory symptoms.

– Arthralgias and arthritis are common among adults, particularly women.

• Congenital infection: Congenital rubella infection can lead to a number of physical defects, usually involving the eyes (e.g., cataracts), ears (e.g., deafness), and heart (e.g., pulmonary arterial stenosis).

– Up to 90% of women infected with rubella virus during the first 11 weeks of pregnancy will deliver an infant with congenital rubella.

– The congenital rubella rate is 20% for maternal infections acquired during the first 20 weeks of pregnancy.


Given the difficulty of diagnosing rubella clinically, serologic testing (for the presence of IgM or a ≥4-fold rise in IgG titer) is generally used for diagnosis.

• If the IgM sample taken within the first 4 days of rash is negative but clinical suspicion remains, testing should be repeated; IgM antibody titers are generally positive for up to 6 weeks.

• Congenital rubella can be diagnosed by detection of IgM antibodies, although titers may be negative during the first month; by isolation of the virus from throat swabs, urine, or CSF; and/or by an IgG titer that does not decline at the expected rate of a twofold dilution per month.

• In the U.S., screening of pregnant women for rubella IgG antibodies is part of routine prenatal care; seronegative women should be vaccinated postpartum.


Symptom-based treatment for various manifestations, such as fever and arthralgia, is appropriate. No rubella-specific therapies are available.


As of 2008, 66% of countries holding membership in the WHO had recommended inclusion of a rubella-containing vaccine in the routine childhood vaccination schedule. One dose induces seroconversion in ≥95% of persons >1 year of age and provides long-term (potentially life-long) immunity.

• Pregnant women should not receive the vaccine, and pregnancy should be avoided for at least 28 days after vaccination.

• Immunoglobulin does not prevent rubella virus infection after exposure and therefore is not recommended as routine postexposure prophylaxis.


Definition and Microbiology

Mumps is an acute systemic communicable viral infection whose most distinctive feature is swelling of one or both parotid glands. It is caused by mumps virus, a negative-strand nonsegmented RNA paramyxovirus.


The estimated annual global incidence of mumps is 100–1000 cases per 100,000 population in countries without national mumps vaccination programs. In the U.S., there were <300 cases in 2001 because levels of childhood vaccination are high.

• The incubation period of mumps is ~19 days, and humans are the only natural hosts.

• Mumps virus is transmitted by respiratory secretions and fomites. Pts are contagious from 1 week before to 1 week after symptom onset and are most contagious 1–2 days before symptom onset.

Clinical Manifestations

Up to half of infections are asymptomatic or lead to nonspecific respiratory symptoms. Unilateral or bilateral parotitis lasting >2 days is present in 70–90% of symptomatic infections.

• A prodrome involving low-grade fever, malaise, myalgia, headache, and anorexia may precede the development of parotitis and last for 1–7 days.

– Pts with parotitis typically have difficulty eating, swallowing, and/or talking and may have an earache.

– Glandular swelling disappears within 1 week.

• Epididymo-orchitis is the second most common manifestation of mumps, developing in 15–30% of cases in postpubertal males.

– Orchitis, characterized by a painful, tender, and enlarged testis, is bilateral in 10–30% of cases and resolves within 1 week.

– Oophoritis (manifested by lower abdominal pain and vomiting) occurs in ~5% of women with mumps.

– Sterility after mumps is rare.

• Symptomatic CNS disease (e.g., aseptic meningitis) occurs in <10% of pts and is usually self-limited.

– In CSF pleocytosis, neutrophils often predominate in the first 24 h before being replaced by lymphocytes on the second day.

– Cranial nerve palsies occasionally lead to permanent sequelae, particularly deafness.

• Other, less common manifestations of mumps include pancreatitis, myocarditis, thyroiditis, nephritis, and arthritis. Mumps in pregnancy does not appear to lead to premature birth, low birth weight, or fetal malformations.


Laboratory diagnosis is generally based on detection of viral antigens or RNA in clinical samples (e.g., throat swab, CSF, urine, seminal fluid) via immunofluorescence or reverse-transcription PCR. Serologic assays are of limited utility since IgM is detected in <20% of cases in immunized pts and IgG titers often exhibit little fluctuation between acute- and convalescent-phase samples.


Mumps is generally a benign, self-resolving illness in which symptom-based and supportive therapies are most helpful.


Current U.S. recommendations are for a two-dose vaccination schedule, with the first dose at ≥1 year old and the second dose at least 1 month after the first. Outbreaks, such as those occurring in 2006 in the U.S., the United Kingdom, and Canada, demonstrate that vaccine-induced immunity is not life-long.



Parvovirus B19 (B19V), a nonenveloped single-strand DNA virus of the family Parvoviridae, is the only member of this family shown definitively to be a human pathogen.


B19V exclusively infects humans, is endemic worldwide, and is transmitted via the respiratory route. By the age of 15 years, ≥50% of children are sero-positive. Of elderly pts, >90% have detectable antibody.


B19V replicates in erythroid progenitors, which are among the few cells that express the B19V receptor, blood group P antigen (globoside). Infection leads to high-titer viremia and arrest of erythropoiesis. When an IgM and IgG antibody response is mounted, normal erythropoiesis resumes.

Clinical Manifestations

Most B19V infections are asymptomatic or are associated with only a mild nonspecific illness.

• Erythema infectiosum (fifth disease): The main manifestation of symptomatic B19V disease, erythema infectiosum presents as a low-grade fever ~7–10 days after exposure and a facial “slapped-cheek” rash (more common among children) a few days later. Two or three days after the facial rash develops, a lacy, reticular macular rash may spread to the extremities.

• Polyarthropathy syndrome: Arthralgias, typically symmetric and affecting the small joints of the hands and occasionally the ankles, knees, and wrists, occur in ~50% of adults (more commonly women). Most cases resolve in a few weeks, but some persist for months.

• Transient aplastic crisis (TAC): Pts with chronic hemolytic conditions (e.g., hemoglobinopathies, autoimmune hemolytic anemia) can develop aplastic crisis with B19V infection that can be life-threatening. Pts display symptoms associated with severe anemia.

• Pure red-cell aplasia/chronic anemia: Immunosuppressed pts can develop persistent anemia with reticulocytopenia, high levels of B19V DNA in serum, and absent or low levels of B19V IgG. B19V occasionally causes a hemophagocytic syndrome.

• Hydrops fetalis: B19V infection during pregnancy can lead to hydrops fetalis and/or fetal loss. The risk of transplacental fetal infection is ~30%, and the risk of fetal loss (which occurs predominantly early in the second trimester) is ~9%. The risk of congenital infection is <1%.


Diagnosis in immunocompetent pts generally relies on detection of B19V-specific IgM antibodies, which can be detected coincident with the rash in erythema infectiosum or by day 3 of TAC.

• B19V-specific IgG is detectable by the seventh day of illness and persists for life.

• Detection of B19V DNA via quantitative PCR should be used to diagnose early TAC or chronic anemia. In acute infection, the viremia load can be >1012 B19V DNA IU/mL of serum; pts with TAC or chronic anemia generally have >105 B19V IU/mL.

TREATMENT Parvovirus Infection

• Treatment of B19V infection is generally supportive as no specific therapy exists. TAC should be treated with transfusions as needed.

• In pts receiving immunosuppressive agents, treatment should be reduced to the extent feasible to allow an immune response. IV immunoglobulin (400 mg/kg daily for 5–10 days) may cure or ameliorate persistent B19V infection in immunosuppressed pts.


For a more detailed discussion, see Brown KE: Parvovirus Infections, Chap. 184, p. 1478; Moss WJ: Measles (Rubeola), Chap. 192, p. 1600; Zimmerman LA, Reef SE: Rubella (German Measles), Chap. 193, p. 1605; and Rubin S, Carbone KM: Mumps, Chap. 194, p. 1608, in HPIM-18.