Pediatric Rubella Follow-up

Infants with complicated congenital rubella syndrome who develop respiratory distress need to be admitted to a neonatal intensive care unit (NICU) for management of hypoxia and, if necessary, ventilatory support.

Some babies may develop severe feeding problems necessitating nasogastric or gastrostomy tube feeding.

Significant hyperbilirubinemia may require inpatient treatment with phototherapy or exchange transfusion.

Outpatient follow-up care is not necessary for patients with postnatal rubella.

Careful follow-up care after discharge from the hospital for patients with congenital rubella syndrome is composed of the following:

• Hearing evaluation
• Vision screening
• Developmental screening

Monitor blood sugar levels and perform thyroid function tests when clinically indicated.

Education and rehabilitation follow-up care are important for children with congenital rubella.

All persons who have contact with patients infected with rubella or children with congenital rubella syndrome (eg, caregivers, household contacts, medical personnel, laboratory workers) should be immune to rubella to prevent rubella outbreaks from persons infected with rubella virus.

Isolation of hospitalized patients

Droplet precautions and standard precautions are recommended for 7 days after the onset of rash in patients with postnatally acquired rubella infections. Contact isolation is indicated for children with proven or suspected congenital rubella infection until they are aged at least 1 year unless nasopharyngeal swab and urine cultures after age 3 months are repeatedly negative for rubella virus. Some authorities suggest that an infant should be considered infectious until 2 cultures of clinical specimens obtained 1 month apart are negative for rubella virus.

School and child care centers

Children diagnosed with postnatal rubella should be excluded from school or child care centers for 7 days after onset of the rash.

Rubella vaccine

Rubella infection may be acquired from an infected asymptomatic person or from a patient during the incubation period for which infected persons may begin to shed the virus and, therefore, are contagious before the onset of symptoms. As a result, the most effective preventive strategy for rubella infection is the administration of rubella vaccine.

In the United States, the only licensed rubella vaccine since 1979 is the 27/3 strain, which is grown in human diploid cell cultures. It is available in 3 forms: as a combined vaccine with measles, mumps, and rubella (MMR), which is most widely used; a combined vaccine with measles, mumps, rubella, and varicella (MMRV), licensed by the US Food and Drug Administration on September 6, 2005; and in monovalent rubella vaccine, which is less frequently used. All 3 forms of vaccine are administered by subcutaneous injection at a standard dose of 0.5 mL.

After administration of a single dose of rubella vaccine, protective serum antibody develops in at least 95% of recipients older than 1 year. Studies have shown that a single dose confers long-term immunity, probably lifelong immunity, against clinical and asymptomatic infection in more than 90% of immunized persons.

MMR vaccine recommendation

Children receive 2 doses of MMR vaccine. The first dose of MMR is received at age 12-15 months. The second dose of MMR is received at age 4-6 years. Children who have not received the second dose by the time they enter school should receive it as soon as possible but no later than age 11-12 years. Guidelines for immunization have been established.^[6]

Persons who have not received at least 1 dose of the vaccine or who have no serologic evidence of immunity to rubella are susceptible to rubella and should be immunized with MMR vaccine. MMR vaccine is especially recommended for all adults at risk of rubella infection (eg, college students, military recruits, health care personnel).

Although birth before 1957 generally is considered presumptive evidence of rubella immunity, serologic surveys of hospital workers indicate that approximately 6% of those born before 1957 do not have detectable rubella antibody. Therefore, health care facilities should consider recommending a dose of MMR vaccine to unvaccinated personnel (whether born before or after 1957) who do not have serologic evidence of rubella immunity.

All postpubertal females without documentation of immunity should be vaccinated unless they are known to be pregnant. Birth before 1957 or clinical diagnosis of rubella is not acceptable evidence of infection for women who could become pregnant because it is only presumptive evidence, not proof, of immunity. Women who receive the vaccine should be counseled not to become pregnant within 28 days of vaccine administration.

Routine serologic testing is not recommended before administering the vaccine.

Precautions and contraindications of MMR vaccine

Because immunoglobulin (Ig) preparations may interfere with the serologic response of rubella and the other components of MMR, the vaccine should be deferred to a later date depending on the dose and the type of Ig given. For instance, patients receiving high doses of Ig (1600-2000 mg/kg body weight), such as those given for treatment of Kawasaki disease and idiopathic thrombocytopenic purpura (ITP), should wait as long as 11 months before receiving MMR. Conversely, patients receiving low doses (eg, 10 mg/kg used in hepatitis B prophylaxis) should wait only 3 months before receiving MMR vaccine (refer to table 3.33 on page 423 of 2003 Red Book: Report of the Committee on Infectious Diseases for all suggested intervals).

Enhanced replication of vaccine viruses may occur in persons who have immune deficiency diseases and in other persons with immunosuppression. Severe immunosuppression may be caused by many disease conditions, such as congenital immunodeficiency, HIV infection, and hematologic or generalized malignancy, and by therapy with immunosuppressive agents (eg, large doses of corticosteroids). For some of these conditions, all affected persons are severely immunocompromised. For other conditions, such as HIV infection, the degree to which the immune system is compromised depends on the severity of the condition, which, in turn, depends on the disease or treatment stage. Ultimately, the patient's physician must assume the responsibility for determining whether the patient is severely immunocompromised on the basis of clinical or laboratory assessment.

The combined MMRV vaccine (ProQuad) has been shown to be associated with an increased risk of febrile seizure occurring 5-12 days following vaccination at a rate of 1 in 2300-2600 in children aged 12 -23 months compared with separate MMR vaccine and varicella vaccine administered simultaneously.^{[7, 8]} As a result, the CDC Advisory Committee on Immunization Practices (ACIP) recommends that separate MMR and varicella vaccines be used for the first dose, although providers or parents may opt to use the combined MMRV for the first dose after counseling regarding this risk.^[9] MMRV is preferred for the second dose (at any age) or the first dose if given at age 48 months or older.

It is estimated that there is a slightly higher risk of febrile seizures in children aged 12-23 months vaccinated with the MMRV when compared with separate MMR and varicella vaccine administration. The period of risk for febrile seizures is from 5-12 days after receipt of the vaccine. However, there is no increased risk of febrile seizures among patients aged 4-6 years receiving the MMRV. Thus, the American Academy of Pediatrics recommends that either MMR and varicella vaccines separately or the MMRV be used for the first dose of measles, mumps, rubella, and varicella vaccines administered at age 12-47 months. For the first dose of measles, mumps, rubella, and varicella vaccines administered at ages 48 months and older, and for dose 2 at any age (15 mo to 12 y), use of MMRV is preferred.^[10]

Data from postlicensure studies do not suggest that children aged 4-6 years who received the second dose of MMRV vaccine had an increased risk for febrile seizures after vaccination compared with children the same age who received MMR vaccine and varicella vaccine administered as separate injections at the same visit.^[9]

Persons infected with HIV

MMR should be administered to all asymptomatic persons infected with HIV who do not have evidence of severe immunosuppression (CD4 >15%). It also should be considered for all symptomatic persons infected with HIV who do not have evidence of severe immunosuppression (see Table 3) because persons infected with HIV are at increased risk of severe complications if infected with the natural strain of rubella virus.

The benefit of immunizing nonseverely immunosuppressed patients infected with HIV with MMR vaccine outweighs any vaccine adverse effects. Studies have shown that the immunologic response to live-antigen and killed-antigen vaccines may decrease as HIV progresses and that vaccination early in the course of HIV infection may be more likely to induce an immune response. Therefore, immunizing infants infected with HIV without severe immunosuppression with MMR vaccine as soon as possible after age 1 year is important. Consideration should be given to administration of the second dose of MMR vaccine as soon as 28 days after the first dose rather than waiting until the child is ready to enter kindergarten or first grade.

Table 3. Age-Specific CD4⁺ T-lymphocyte Count and Percentage of Total Lymphocytes as a Criteria for Severe Immunosuppression in Persons with HIV (Open Table in a new window)

Steroids

Systemically absorbed steroids can suppress the immune system in an otherwise healthy person. However, neither the dose nor the duration of therapy sufficient to cause immune suppression is well defined. Many experts agree that live virus vaccines, such as MMR and its components, may still be given when (1) steroid therapy is short term (ie, < 14 d) with low-to-moderate doses, (2) low-to-moderate doses are administered daily or on alternate days, (3) long-term alternate-day treatment involves short-acting preparations, (4) steroids are used as physiologic maintenance for replacement therapy, and (5) steroids are administered topically (eg, eyes, skin), by aerosol, or by intraarticular, bursal, or tendon injection.

Most clinicians agree that persons who have received systemic steroid doses of more than or equivalent to a prednisone dose of 2 mg/kg of body weight or a total dose of 20 mg administered daily or on alternate days for an interval of more than 14 days should avoid vaccination with MMR for at least 1 month following the cessation of steroid therapy.

Persons who receive steroid doses of more than or equivalent to prednisone doses of 2 mg/kg or 20 mg total dose daily or on alternate days for an interval of less than 14 days generally can receive MMR, although some experts prefer waiting until 2 weeks after completion of therapy.

Persons who have received prolonged or extensive topical, aerosol, or other local corticosteroid therapy that causes clinical or laboratory evidence of systemic immunosuppression should also avoid vaccination with MMR for at least 1 month.

Leukemia

Persons with leukemia in remission who were not immune to measles, rubella, or mumps when leukemia was diagnosed may receive MMR or its component vaccines. For individuals who have received chemotherapy, MMR vaccine can be given 3 months after termination of chemotherapy and the patient's immune status recovery.

Pregnancy

MMR should not be given to pregnant women because of the theoretical risk of rubella infection to the fetus.

Data collected by the CDC reveal the estimated risk to be 1.6%. However, no cases of congenital defects have been reported in the offspring of women who inadvertently received the vaccine in their first trimester of pregnancy.

Healthcare providers should routinely conduct a rubella IgG test for all pregnant women at the earliest prenatal visit. A positive rubella IgG antibody test indicates rubella immunity.

Pregnant women who are found to be susceptible should be monitored for signs of rubella during pregnancy and should be advised to avoid contact with persons with rash illness.

Rubella vaccine should be administered to nonimmune persons upon completion of pregnancy, preferably prior to discharge from the hospital.

Guidelines for rubella in pregnancy have been established.^[11]

Severe illness

Generally, vaccination of persons with moderate or severe febrile illness should be deferred until they have recovered from the acute phase of their illness to avoid superimposing adverse effects of vaccination on the underlying illness or mistakenly attributing a manifestation of the underlying illness to the vaccine.

Allergies

Rubella virus strain contained in MMR is grown in human diploid cell cultures, while the other 2 components, measles and mumps virus strains, are produced in chick embryo fibroblasts but do not contain significant amounts of egg white (ovalbumin) cross-reacting proteins. MMR also contains hydrolyzed gelatin as a stabilizer and trace amounts of neomycin. Anaphylactic reaction to MMR is rare. Recent data indicate that allergic reactions are mostly caused by other components of the vaccine, such as gelatin and neomycin.

Among persons who are allergic to eggs, the risk of serious allergic reactions, such as anaphylaxis, following administration of MMR is extremely low. For this reason, skin testing with vaccine is not predictive of allergic reactions to the vaccination and, therefore, is not required before administering MMR to persons who are allergic to eggs. Similarly, the administration of gradually increasing doses of vaccine is not required.

Nonanaphylactic reactions to MMR, such as urticaria and contact dermatitis, are not contraindications to immunization.

Children who developed a significant hypersensitivity reaction following the first dose of MMR vaccine should have serologic testing to determine immunity to the component of the vaccines. If shown to be immune, they should not receive a second dose of the vaccine. If the second dose is necessary, these children should have adequate evaluation for possible serious reaction to the vaccine, and skin testing should be considered before administration of the vaccine.

MMR immunization is contraindicated in children who have had immediate anaphylactic reaction following previous administration of the vaccine. However, these patients require serologic testing to determine whether they are immune to the components of the vaccine.

In case of history of anaphylactic reaction to topically or systematically administered neomycin, consultation with an allergist or immunologist is warranted. In addition, MMR should be administered only in settings where such reactions could be properly managed.

Adverse reactions to MMR

Fever of 39.4°C (103°F) or higher may develop in 5-15% of vaccine recipients from 5-12 days after immunization.

Rash develops in 5% of patients 7-10 days after vaccination.

Mild lymphadenopathy is common.

Joint pain is observed in 0.5% of young children.

Arthralgia is experienced in 25% of females who are past puberty.

Transient arthritis occurs in 10% of females who are past puberty.

Joint complaints occur approximately 7-21 days following MMR vaccination.

Rare cases of transient peripheral neuritic symptoms, such as paresthesia and pain in the arms and legs, have been reported.

Transient and benign thrombocytopenia within 2 months of immunization has been reported in 1 per 25,000-40,000 immunized children.

CNS manifestations have also been reported, but no causal relationship with rubella vaccine has been demonstrated.

Joint involvement

Arthralgia and arthritis are the most common complications of rubella in adolescents and adults. Females are affected 4-5 times more frequently than males. The joints are involved in up to one third of adult women; the fingers, wrists, knees, and ankles are the most frequently involved. Massive effusions often accompany rubella arthritis, and symptoms may persist for 10-14 days. Arthralgia usually begins with the onset of the rash and clears without sequelae within 2-30 days.

Thrombocytopenia

This is a rare complication, occurring in 1 per 3000 cases. Children are affected more frequently than adults, and girls are affected more often than boys. It is self-limited and lasts from a few days to several months.

Neurologic manifestations

Encephalitis is a rare complication and occurs with greater frequency in children. It occurs in 1 per 5000 cases and usually is observed 2-4 days after the onset of rash. In some patients, encephalitis may accompany the rash or be delayed as much as 1 week after onset of the exanthem. CSF examination usually reveals mild pleocytosis (20-100 WBC/mcL) with predominance of lymphocytes. Glucose level is usually normal, while protein levels may be normal or slightly elevated. Rubella encephalitis usually resolves with little or no significant neurologic sequelae.

Mild hepatitis has been a rarely reported complication of acquired rubella.

The prognosis of postnatal rubella is good with full recovery, while congenital rubella syndrome may have a poor outcome with severe multiple-organ damage.

All pregnant women should avoid any contact with persons infected with rubella.

All susceptible individuals should be immunized.

No special precaution is necessary in the household setting of a child with congenital rubella syndrome, although parents should be counseled regarding potential serious risk to pregnant women exposed to the child.

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