Etiology

Measles (rubeola) is caused by a single-stranded RNA paramyxovirus with one antigenic type. Humans are the only natural host. Measles virus infects the upper respiratory tract and regional lymph nodes and is spread systemically during a brief, low-titer primary viremia. A secondary viremia occurs within 5 to 7 days as virus-infected monocytes spread the virus to the respiratory tract, skin, and other organs. Virus is present in respiratory secretions, blood, and urine of infected individuals. Measles virus is transmitted by large droplets from the upper respiratory tract and requires close contact. The virus is stable at room temperature for 1 to 2 days. Infected persons are contagious from 1 to 2 days before onset of symptoms (about 5 days before onset of rash) to 4 days after the appearance of the rash.

Epidemiology

Measles is endemic in regions of the world where measles vaccination is not available and is responsible for about 1 million deaths per year. Since 2000, there typically have been fewer than 100 cases reported annually in the United States, although outbreaks occur. Infections of nonimmigrant children during outbreaks may occur as a result of age (too young to be vaccinated) or low immunization rates. Most young infants are protected by transplacental antibody, but infants become susceptible toward the end of the first year of life.

Clinical Manifestations

Measles infection is divided into four phases: incubation, prodromal (catarrhal), exanthematous (rash), and recovery. The incubation period is 8 to 12 days from exposure to the onset of symptoms and 14 days from exposure to the onset of rash. The manifestations of the 3-day prodromal period are cough, coryza, conjunctivitis, and the pathognomonic Koplik spots (gray-white, sand grain–sized dots on the buccal mucosa opposite the lower molars) that last 12 to 24 hours. The conjunctiva may reveal a characteristic transverse line of inflammation along the eyelid margin (Stimson line).The classic symptoms of cough, coryza, and conjunctivitis occur during the secondary viremia of the exanthematous phase, which often is accompanied by high fever (40° C to 40.5° C [104° F to 105° F]). The macular rash begins on the head (often above the hairline) and spreads over most of the body in 24 hours in a cephalad to caudal pattern. Areas of the rash often are confluent. The rash fades in the same pattern. The severity of the illness is related to the extent of the rash. It may be petechial or hemorrhagic (black measles). As the rash fades, it undergoes brownish discoloration and desquamation.

Cervical lymphadenitis, splenomegaly, and mesenteric lymphadenopathy with abdominal pain may be noted with the rash. Otitis media, pneumonia, and diarrhea are more common in infants. Liver involvement is more common in adults.

The term modified measles describes mild cases of measles occurring in persons with partial protection against measles. Modified measles occurs in persons vaccinated before 12 months of age or with coadministration of immune serum globulin, in infants with disease modified by transplacental antibody, or in persons receiving immunoglobulin.

Laboratory and Imaging Studies

Routine laboratory findings are nonspecific and do not aid in diagnosis. Leukopenia is characteristic. In patients with acute encephalitis, the cerebrospinal fluid reveals an increased protein, a lymphocytic pleocytosis, and normal glucose levels. Measles virus culture is not generally available. Serologic testing for IgM antibodies, which appear within 1 to 2 days of the rash and persist for 1 to 2 months, confirms the clinical diagnosis. Chest x-rays may show interstitial or perihilar infiltrates but may indicate measles pneumonia or bacterial superinfection. Suspected cases should immediately be reported to the local or state health department.

Differential Diagnosis

The constellation of fever, rash, cough, and conjunctivitis is diagnostic for measles. Koplik spots are pathognomonic but are not always present at the time the rash is most pronounced. Confirmation is by identification of multinucleated giant cells in nasal mucosal smears and diagnostic antibody increases in acute and convalescent serum. The rash must be differentiated from rubella, roseola, enteroviral or adenoviral infection, infectious mononucleosis, toxoplasmosis, meningococcemia, scarlet fever, rickettsial disease, Kawasaki syndrome, serum sickness, and drug rash.

Treatment

Routine supportive care includes maintaining adequate hydration and antipyretics. High-dose vitamin A supplementation improves the outcome of malnourished infants with measles and should be considered for persons at high risk for severe complications, including hospitalized infants 6 months to 2 years of age as well as immunodeficient children. The World Health Organization and United Nations and International Children’s Emergency Fund recommend routine administration of vitamin A therapy in areas with known vitamin A deficiency or a measles case fatality rate of greater than 1%.

Complications and Prognosis

Otitis media is the most common complication of measles infection. Interstitial (measles) pneumonia or pneumonia may result from secondary bacterial infection with Streptococcus pneumoniae, Staphylococcus aureus, or group A streptococcus. Persons with impaired cell-mediated immunity may develop giant cell (Hecht) pneumonia, which is usually fatal. Anergy associated with measles may activate latent tuberculosis. Myocarditis and mesenteric lymphadenitis are infrequent complications.

Encephalomyelitis occurs in 1 to 2 per 1000 cases and usually occurs 2 to 5 days after the onset of the rash. Early encephalitis probably is caused by direct viral infection of brain tissue, whereas later onset encephalitis is a demyelinating and probably an immunopathologic phenomenon. Subacute sclerosing panencephalitis is a late neurologic complication of slow measles infection that is characterized by progressive behavioral and intellectual deterioration and eventual death. It occurs in approximately 1 in every 1 million cases of measles, an average of 8 to 10 years after measles. There is no effective treatment.

Deaths most frequently result from bronchopneumonia or encephalitis, with much higher risk in persons with malignancy or human immunodeficiency virus (HIV) infection. Deaths in adolescents and adults usually result from subacute sclerosing panencephalitis. Other forms of measles encephalitis in immunocompetent persons are associated with a mortality rate of approximately 15%, with 20% to 30% of survivors having serious neurologic sequelae.

Prevention

Live measles vaccine prevents infection and is recommended as measles, mumps, and rubella (MMR) for children at 12 to 15 months and 4 to 6 years of age. The MMRV (MMR combined with varicella vaccine) is an alternative vaccine for children 12 months to 12 years of age, provided there are no contraindications. The second dose of MMR is not a booster dose but significantly reduces the primary vaccine failure rate, which is less than 5%. Contraindications to measles vaccine include immunocompromised states resulting from congenital immunodeficiency, severe HIV infection, leukemia, lymphoma, cancer therapy, or an immunosuppressive course of corticosteroids (>2 mg/kg/day for >14 days); pregnancy; or recent administration of immunoglobulin (3 to 11 months, depending on dose). MMR vaccination is recommended for all HIV-infected persons without evidence of severe immunosuppression (low age-specific total CD4 T-lymphocyte count or a low CD4 T-lymphocyte count as a percentage of total lymphocytes), children with cancer in remission who have not received chemotherapy in the previous 3 months, and children who have not received immunosuppressive corticosteroids in the previous month. Susceptible household contacts with a chronic disease or who are immunocompromised when exposed to measles should receive postexposure prophylaxis with measles vaccine, within 72 hours of exposure, or immunoglobulin within 6 days of exposure.

Etiology

Rubella, also known as German measles or 3-day measles, is caused by a single-stranded RNA virus with a glycolipid envelope, which is a member of the togavirus family. Humans are the only natural host. Rubella virus invades the respiratory epithelium and disseminates via a primary viremia. After replication in the reticuloendothelial system, a secondary viremia ensues, and virus can be isolated from peripheral blood monocytes, cerebrospinal fluid, and urine.

Infection in utero results in significant morbidity from congenital rubella syndrome (see Chapter 66). Maternal infection during the first trimester results in fetal infection and generalized vasculitis in more than 90% of cases. Rubella virus is most contagious from 2 days before until 5 to 7 days after onset of the rash, although virus may be present in nasopharyngeal secretions from 7 days before until 14 days after the rash. Infants with congenital rubella may shed virus in nasopharyngeal secretions and urine for longer than 12 months after birth and may transmit the virus to susceptible contacts.

Epidemiology

In unvaccinated populations, rubella usually occurs in the spring, with epidemics occurring in cycles of every 6 to 9 years. Subclinical cases outnumber clinically apparent cases by a ratio of 2:1. Fewer than 20 cases of rubella occur annually in the United States. Outbreaks of rubella in nonvaccinated groups occasionally occur in adults in workplaces, prisons, colleges, and health care centers from internationally imported cases. Transplacental antibody is protective during the first 6 months of life.

Clinical Manifestations

The incubation period for postnatal rubella is 14 to 23 days. The mild catarrhal symptoms of the prodromal phase of rubella may go unnoticed. The characteristic signs of rubella are retroauricular, posterior cervical, and posterior occipital lymphadenopathy accompanied by an erythematous, maculopapular, discrete rash. The rash begins on the face and spreads to the body and lasts for 3 days. The rash is less prominent than with measles. Rose-colored spots on the soft palate, known as Forchheimer spots, develop in 20% of patients and may appear before the rash. Other manifestations of rubella include mild pharyngitis, conjunctivitis, anorexia, headache, malaise, and low-grade fever. Polyarthritis, usually of the hands, may occur, especially among adult females, but usually resolves without sequelae. Paresthesias and tendinitis may occur.

Laboratory and Imaging Studies

Routine laboratory findings in cases of rubella are nonspecific and generally do not aid in diagnosis. The white blood cell count usually is normal or low, and thrombocytopenia rarely occurs. Diagnosis is confirmed by serologic testing for IgM antibodies or by a fourfold or greater increase in specific IgG antibodies in paired acute and convalescent sera. Cases of suspected congenital rubella syndrome and postnatal rubella infection should be reported to the local and state health department.

Differential Diagnosis

The rash must be differentiated from measles, roseola, enteroviral or adenoviral infection, infectious mononucleosis, toxoplasmosis, scarlet fever, rickettsial disease, Kawasaki syndrome, serum sickness, and drug rash.

Treatment

There is no specific therapy for rubella. Routine supportive care includes maintaining adequate hydration and antipyretics.

Complications and Prognosis

Complications of rubella are rare. Rubella infection during pregnancy may result in congenital rubella syndrome with intrauterine growth retardation, cataracts, deafness, neurologic deficits, and a patent ductus arteriosus (see Chapter 66). The prognosis for rubella is excellent. Deaths rarely occur with rubella encephalitis.

Prevention

Live rubella vaccine prevents infection and is recommended as MMR for children at 12 to 15 months and at 4 to 6 years of age. After vaccination, rubella virus is shed from the nasopharynx for several weeks, but it is not communicable. Pregnant women who are susceptible to rubella should be immunized after delivery. In children, rubella vaccine rarely is associated with adverse effects, but in postpubertal females, it causes arthralgias in 25% of vaccinees and acute arthritis-like symptoms in 10% of vaccinees. These symptoms typically develop 1 to 3 weeks after vaccination and last 1 to 3 days.

Contraindications to rubella vaccine include immunocompromised states resulting from congenital immunodeficiency, HIV infection, leukemia, lymphoma, cancer therapy, or an immunosuppressive course of corticosteroids (>2 mg/kg/day for >14 days); pregnancy; or recent administration of immunoglobulin (3 to 11 months, depending on dose). Vaccine virus has been recovered from fetal tissues, although no cases of congenital rubella syndrome have been identified among infants born to women inadvertently vaccinated against rubella in pregnancy. Nevertheless, women are cautioned to avoid pregnancy after receipt of rubella-containing vaccine for 28 days. All pregnant women should have prenatal serologic testing to determine their immune status to rubella, and susceptible mothers should be vaccinated after delivery and before hospital discharge.

Susceptible, nonpregnant persons exposed to rubella should receive rubella vaccination. Immunoglobulin should be administered to susceptible, pregnant women exposed to rubella.

Etiology

Roseola infantum (exanthem subitum, sixth disease) is caused primarily by human herpesvirus type 6 (HHV-6), and by HHV-7 in 10% to 30% of cases. HHV-6 and HHV-7 are large, enveloped double-stranded DNA viruses that are members of the herpesvirus family. They infect mature mononuclear cells and cause a relatively prolonged (3 to 5 days) viremia during primary infection. They can be detected in the saliva of healthy adults, which suggests, as with other herpesviruses, the development of lifelong latent infection and intermittent shedding of virus.

Epidemiology

Transplacental antibody protects most infants until 6 months of age. The incidence of infection increases as maternally derived antibody levels decline. By 12 months of age, approximately 60% to 90% of children have antibodies to HHV-6, and essentially all children are seropositive by 2 to 3 years of age. The virus is likely acquired from asymptomatic adults who periodically shed these viruses. HHV-6 is a major cause of acute febrile illnesses in infants and may be responsible for 20% of visits to the emergency department for children 6 to 18 months of age.

Clinical Manifestations

Roseola is characterized by high fever (often >40° C) with an abrupt onset that lasts 3 to 5 days. A maculopapular, rose-colored rash erupts coincident with defervescence, although it may be present earlier. The rash usually lasts 1 to 3 days but may fade rapidly and is not present in all infants with HHV-6 infection. Upper respiratory symptoms, nasal congestion, erythematous tympanic membranes, and cough may occur. Gastrointestinal symptoms are described. Most children with roseola are irritable and appear toxic. Roseola is associated with approximately one third of febrile seizures. Roseola caused by HHV-6 and HHV-7 is clinically indistinguishable, although HHV-6–associated roseola typically occurs in younger infants. Reactivation of HHV-6 following bone marrow transplantation may result in bone marrow suppression.

Laboratory and Imaging Studies

Routine laboratory findings are nonspecific and do not aid in diagnosis. Encephalitis with roseola is characterized by pleocytosis (30 to 200 cells/mm³) with mononuclear cell predominance, elevated protein concentration, and normal glucose concentration. Serologic testing showing a fourfold rise in acute and convalescent sera or documenting HHV-6 DNA by polymerase chain reaction in the cerebrospinal fluid is diagnostic.

Differential Diagnosis

The pattern of high fever for 3 to 5 days without significant physical findings followed by onset of rash with defervescence of fever is characteristic. Many febrile illnesses may be easily confused with roseola during the pre-eruptive stage. Serious infections must be excluded, although most children are alert, behave normally, and continue with their usual daily activities.

Treatment

There is no specific therapy for roseola. Routine supportive care includes maintaining adequate hydration and antipyretics.

Complications and Prognosis

The prognosis for roseola is excellent. A few deaths have been attributed to HHV-6, usually in cases complicated by encephalitis or virus-associated hemophagocytosis syndrome.

Prevention

There are no guidelines for prevention of roseola.

Etiology

Erythema infectiosum (fifth disease) is caused by the human parvovirus B19, a single-stranded DNA virus producing a benign viral exanthem in healthy children. The affinity of this virus to red blood cell progenitor cells makes it an important cause of aplastic crisis in patients with hemolytic anemias, including sickle cell disease, spherocytosis, and thalassemia. Parvovirus B19 also causes fetal anemia and hydrops fetalis after primary infection during pregnancy. The cell receptor for parvovirus B19 is the erythrocyte P antigen, a glycolipid present on erythroid cells. The virus replicates in actively dividing erythroid stem cells, leading to cell death that results in erythroid aplasia and anemia.

Epidemiology

Erythema infectiosum is common. Parvovirus B19 seroprevalence is only 2% to 9% in children younger than 5 years of age, but it increases to 15% to 35% in children 5 to 18 years and 30% to 60% in adults. Community epidemics usually occur in the spring. The virus is transmitted by respiratory secretions and by blood product transfusions.

Clinical Manifestations

The incubation period is typically 4 to 14 days and rarely may last 21 days. Parvovirus B19 infections usually begin with a mild, nonspecific illness characterized by fever, malaise, myalgias, and headache. In some cases, the characteristic rash appears 7 to 10 days later. Erythema infectiosum is manifested by rash, low-grade or no fever, and occasionally pharyngitis and mild conjunctivitis. The rash appears in three stages. The initial stage is typically a “slapped cheek” rash with circumoral pallor. An erythematous symmetrical, maculopapular, truncal rash appears 1 to 4 days later, then fades as central clearing takes place, giving a distinctive lacy, reticulated rash that lasts 2 to 40 days (mean, 11 days). This rash may be pruritic, does not desquamate, and may recur with exercise, bathing, rubbing, or stress. Adolescents and adults may experience myalgia, significant arthralgia or arthritis, headache, pharyngitis, coryza, and gastrointestinal upset.

Children with shortened erythrocyte life span (e.g., sickle cell disease) may develop a transient aplastic crisis characterized by ineffective erythroid production (see Chapter 150). Most children with parvovirus B19–induced transient aplastic crisis have multiple symptoms, including fever, lethargy, malaise, pallor, headache, gastrointestinal symptoms, and respiratory symptoms. The reticulocyte count is extremely low or zero, and the hemoglobin level is lower than usual for the patient. Transient neutropenia and thrombocytopenia also commonly occur.

Persistent parvovirus B19 infection may develop in children with immunodeficiency, causing severe anemia resulting from pure red blood cell aplasia. These children do not display the typical manifestations of erythema infectiosum.

Laboratory and Imaging Studies

Many abnormalities occur with parvovirus infection, including reticulocytopenia lasting 7 to 10 days, mild anemia, thrombocytopenia, lymphopenia, and neutropenia. Parvovirus B19 can be detected by polymerase chain reaction and by electron microscopy of erythroid precursors in the bone marrow. Serologic tests showing antibody response to parvovirus, especially the presence of specific IgM antibody to parvovirus, are diagnostic.

Differential Diagnosis

The diagnosis of erythema infectiosum in children is established on the basis of the clinical findings of typical facial rash with absent or mild prodromal symptoms, followed by a reticulated rash over the body that waxes and wanes. The differential diagnosis includes measles, rubella, scarlet fever, enteroviral or adenoviral infection, infectious mononucleosis, scarlet fever, Kawasaki disease, systemic lupus erythematosus, serum sickness, and drug reaction.

Treatment

There is no specific therapy. Routine supportive care includes maintaining adequate hydration and antipyretics. Transfusions may be required for transient aplastic crisis. Intrauterine transfusion has been performed for hydrops fetalis associated with fetal parvovirus B19 infection. Intravenous immunoglobulin may be used for immunocompromised persons with severe anemia.

Complications and Prognosis

The prognosis for erythema infectiosum is excellent. Fatalities associated with transient aplastic crisis are rare. Parvovirus B19 is not teratogenic, but in utero infection of fetal erythroid cells may result in fetal heart failure, hydrops fetalis, and fetal death. Of the approximately 50% of women of childbearing age susceptible to parvovirus B19 infection, 30% of exposed women develop infection, with 25% of exposed fetuses becoming infected and 10% of these culminating in fetal death.

Prevention

The greatest risk is to pregnant women. Effective control measures are limited. Exclusion of affected children from school is not recommended, because children generally are not infectious by the time the rash is present. Good handwashing and hygiene are practical measures that should help reduce transmission.

Etiology

Chickenpox and zoster are caused by varicella-zoster virus (VZV), an enveloped, icosahedral, double-stranded DNA virus that is a member of the herpesvirus family. Humans are the only natural host. Chickenpox (varicella) is the manifestation of primary infection. VZV infects susceptible individuals via the conjunctivae or respiratory tract and replicates in the nasopharynx and upper respiratory tract. It disseminates by a primary viremia and infects regional lymph nodes, the liver, the spleen, and other organs. A secondary viremia follows, resulting in a cutaneous infection with the typical vesicular rash. After resolution of chickenpox, the virus persists in latent infection in the dorsal root ganglia cells. Zoster (shingles) is the manifestation of reactivated latent infection of endogenous VZV. Chickenpox is highly communicable in susceptible individuals, with a secondary attack rate of more than 90%. The period of communicability ranges from 2 days before to 7 days after the onset of the rash, when all lesions are crusted.

Epidemiology

In the prevaccine era, the peak age of occurrence was 5 to 10 years, with peak seasonal infection in late winter and spring. Transmission is by direct contact, droplet, and air. Zoster is a recurrence of latent VZV. Only 5% of cases of zoster occur in children younger than 15 years of age. The overall incidence of zoster (215 cases per 100,000 person-years) results in a cumulative lifetime incidence of approximately 10% to 20%, with 75% of cases occurring after 45 years of age. The incidence of zoster is increased in immunocompromised persons.

Clinical Manifestations

The incubation period of varicella is generally 14 to 16 days, with a range of 11 to 20 days after contact. Prodromal symptoms of fever, malaise, and anorexia may precede the rash by 1 day. The characteristic rash appears initially as small red papules that rapidly progress to nonumbilicated, oval, “teardrop” vesicles on an erythematous base. The fluid progresses from clear to cloudy, and the vesicles ulcerate, crust, and heal. New crops appear for 3 to 4 days, usually beginning on the trunk followed by the head, the face, and, less commonly, the extremities. There may be a total of 100 to 500 lesions, with all forms of lesions being present at the same time. Pruritus is universal and marked. Lesions may be present on mucous membranes. Lymphadenopathy may be generalized. The severity of the rash varies, as do systemic signs and fever, which generally abate after 3 to 4 days.

The pre-eruption phase of zoster includes intense localized and constant pain and tenderness (acute neuritis) along a dermatome, accompanied by malaise and fever. In several days, the eruption of papules, which quickly vesiculate, occurs in the dermatome or in two adjacent dermatomes. Groups of lesions occur for 1 to 7 days and then progress to crusting and healing. Thoracic and lumbar regions are typically involved. Lesions generally are unilateral and are accompanied by regional lymphadenopathy. In one third of patients, a few vesicles occur outside the primary dermatome. Any branch of cranial nerve V may be involved, which also may cause corneal and intraoral lesions. Involvement of cranial nerve VII may result in facial paralysis and ear canal vesicles (Ramsay Hunt syndrome). Ophthalmic zoster may be associated with ipsilateral cerebral angiitis and stroke. Immunocompromised persons may have unusually severe, painful herpes zoster that involves cutaneous and, rarely, visceral dissemination (to liver, lungs, and central nervous system). Postherpetic neuralgia, defined as pain persisting longer than 1 month, is uncommon in children.

Laboratory and Imaging Studies

Laboratory testing confirmation for diagnosis is usually unnecessary. Vesicles exhibit polymorphonuclear leukocytes. Cytology and electron microscopy of vesicular fluid or scrapings may reveal intranuclear inclusions, giant cells, and virus particles. VZV is fastidious and difficult to culture. Cytology consistent with either HSV or VZV in the presence of a negative culture suggests VZV. Detection of varicella-specific antigen in vesicular fluid by immunofluorescence using monoclonal antibodies or demonstration of a fourfold antibody increase of acute and convalescent sera are diagnostic.

Differential Diagnosis

The diagnosis of varicella and zoster is based on the distinctive characteristics of the rash. Eczema herpeticum, or Kaposi varicelliform eruption, is a localized, vesicular eruption caused by HSV that develops on skin affected by underlying eczema or trauma. The differentiation between zoster and HSV infection may be difficult because HSV may cause eruption that appears to be in a dermatomal distribution. Coxsackievirus A infection has a vesiculopustular appearance, but lesions are usually localized to the extremities and oropharynx. A previously healthy patient with more than one recurrence probably has HSV infection, which can be confirmed by viral culture.

Treatment

Symptomatic therapy of varicella includes nonaspirin antipyretics, cool baths, and careful hygiene. Early therapy with antivirals in immunocompromised persons is effective in preventing severe complications, including pneumonia, encephalitis, and death from varicella. Early administration of acyclovir, famciclovir, or valacyclovir for chickenpox may decrease the incidence of varicella pneumonia and is recommended for nonpregnant persons older than 13 years of age and children older than 12 months of age with chronic cutaneous or pulmonary disease; receiving short-course, intermittent, or aerosolized corticosteroids; or receiving long-term salicylate therapy. The dose of acyclovir for VZV infections is much higher than for HSV. Routine oral administration of acyclovir is not recommended in otherwise healthy children with chickenpox because of marginal therapeutic benefit, the lack of difference in complications, and the cost of acyclovir treatment.

Antiviral treatment of zoster accelerates cutaneous healing, hastens the resolution of acute neuritis, and reduces the risk of postherpetic neuralgia. Oral famciclovir and valacyclovir have much greater oral bioavailability than acyclovir and are recommended for treatment of zoster in adults. Acyclovir is recommended for children and is an alternative therapy for adults. The necessity of concomitant oral corticosteroids for zoster is controversial.

Complications and Prognosis

Secondary infection of skin lesions by streptococci or staphylococci is the most common complication. These infections may be mild, resembling impetigo, or life-threatening with toxic shock syndrome or necrotizing fasciitis. Pneumonia is uncommon in healthy children but occurs in 15% to 20% of healthy adults and immunocompromised persons. Myocarditis, pericarditis, orchitis, hepatitis, ulcerative gastritis, glomerulonephritis, and arthritis may complicate varicella. Reye syndrome may follow varicella; thus, aspirin use is contraindicated during varicella infection.

Neurologic complications frequently include postinfectious encephalitis, cerebellar ataxia, nystagmus, and tremor. Less common neurologic complications include Guillain-Barré syndrome, transverse myelitis, cranial nerve palsies, optic neuritis, and hypothalamic syndrome.

Primary varicella can be a fatal disease in immunocompromised persons as a result of visceral dissemination, encephalitis, and pneumonitis. The mortality rate approaches 15% in children with leukemia who do not receive prophylaxis or therapy for varicella (see Chapter 66).

A severe form of neonatal varicella may develop in newborns of mothers with varicella (but not shingles) occurring 5 days before or 2 days after delivery. The fetus is exposed to a large inoculum of virus but is born before the maternal antibody response develops. These infants should be treated as soon as possible with varicella-zoster immunoglobulin (VZIG) to attempt to prevent or ameliorate the infection.

Primary varicella usually resolves spontaneously. The mortality rate is much higher for persons older than 20 years of age and for immunocompromised persons. Zoster usually is self-limited, especially in children. Advanced age and severity of pain at presentation and at 1 month are predictors of prolonged pain. Scarring is more common with zoster because of involvement of the deeper layers of the skin.

Prevention

Children with chickenpox should not return to school until all vesicles have crusted. A hospitalized child with chickenpox should be isolated in a negative-pressure room to prevent transmission.

A live attenuated varicella vaccine—two doses for all children—is recommended. The first dose should be administered at age 12 to 15 months and the second dose at 4 to 6 years. Varicella vaccine is 85% effective in preventing any disease and 97% effective in preventing moderately severe and severe disease. Transmission of vaccine virus from a healthy vaccinee is rare but possible.

Passive immunity can be provided by VZIG, which is indicated within 96 hours of exposure for susceptible individuals at increased risk for severe illness. Administration of VZIG does not eliminate the possibility of disease in recipients and prolongs the incubation period up to 28 days.