Rubella Infection

Sample for Rubella Antibody Tests

1. The Serum of the patient is needed.
2. A random sample can be used.
3. The virus can be found in the washings of the throat.
4. The virus is found in the CSF, urine, amniotic fluid, and other sites in congenital infection.

Purpose of the test (Indications) for Rubella Antibody Tests

1. It diagnoses the rubella infection.
2. It is done to find the immune status of the patient.
3. It is advised in pregnant ladies.
4. It may be advised in low-weight babies.

Rubella history:

1. Historical facts:
   1. Rubella virus was first isolated in 1962.
   2. Three live attenuated vaccine strains were developed and first licensed in the USA  for use in 1969.
   3. In 1964 > 20,000 cases of congenital rubella syndrome and an unknown number of stillbirths occurred in the USA.

Definition of rubella infection:

1. Rubella virus infection is also called German measles.
2. Rubella virus is a single-stranded RNA Rubivirus.
3. This is an acute episodic disease with the onset of generalized maculopapular rashes fever of > 99 F.
   1. Rashes are not prominent as in measles.
   2. There may be arthritis and arthralgia.
   3. Also, there may be lymphadenopathy and conjunctivitis.
   4. Mostly lymphadenopathy involves the posterior occipital area.

Structure of Rubella virus:

1. Rubella is also called German measles or three-day measles.
2. This belongs to the Togavirus group.
3. This is the RNA virus and is 60 nm in diameter.
4. The envelope possesses a hemagglutinin.

Spread of Rubella infection:

1. This is a contagious viral infection.
2. This benign disease is spread by droplet infection and enters the body through the respiratory route.
3. After 3 weeks rash appears, and now the antibody can be demonstrated in the blood.
4. This is best known for its distinctive red rash.
5. Rubella is not the same as measles, called Rubeola, a serious disease.
6. Both of these diseases have common symptoms of rashes.
7. Nowadays, children are given MMR (measles, mumps, and rubella) vaccines.
   1. Children in the United States are given vaccination twice before they reach school age, which is highly effective in preventing rubella.
   2. Children are given MMR first dose at 12 to 15 months of age and the second dose at 4 to 6 years.
   3. CDC has declared rubella eliminated in the United States.

Pathogenesis of Rubella virus infection:

1. There is viremia 5 to 7 days after exposure to the virus, and this virus spreads to various organs and tissues.
2. In the case of pregnancy, if there is an infection, then there are chances for congenital abnormalities in the fetus.
3. There are chances for abortion or stillbirth.
4. 25% to 50% of the cases, the disease is subclinical.

Signs and Symptoms of Rubella infection:

1. The signs and symptoms vary from person to person. The diagnosis may be missed in the case of a mild rash.
   1. Rubella infection may resemble drug-induced rashes and infectious mononucleosis.
2. The incubation period varies from 10 to 21 days, and the typical period is 12 to 14 days.
   1. The infectious patient is contagious for 12 to 15 days, beginning 5 to 7 days before the appearance of the rash.
   2. Acute rubella infection lasts 3 to 5 days and requires little treatment.
3. There is a prodromal period of catarrhal symptoms, followed by retroauricular, posterior cervical, and postoccipital lymphadenopathy.
4. These patients have a fever, usually less than 101 °F, followed by a maculopapular rash for 2 to 3 days.
5. The rash starts on the face and spreads to the rest of the body.

6. The patient may have a sore throat, tiredness, loss of appetite, muscle and body aches, and chills.
7. In older children and adults, self-limiting arthralgia and arthritis are common.

The spread of the Rubella disease:

1. The reservoir is human.
2. The mode of transmission is through:
   1. Person-to-person contact.
   2. It spreads through respiratory tract secretions.
   3. If there is direct contact with the lesion.

Types of Rubella infection:

Acquired infection:

1. The incubation period of acquired rubella infection varies from 10 to 21 days, typically 12 to 14 days.
2. The infected person is contagious for 12 to 15 days, beginning 5 to 7 days before the appearance of a rash (if present).
3. Acute rubella infection lasts from 3 to 5 days and generally requires little treatment.
4. Permanent effects are extremely rare in acquired infections.
5. The clinical presentation of acquired rubella is usually mild.

Congenital infection:

1. Rubella virus is teratogenic if the mother is infected during the first trimester.
   1. During Viremia, viruses cross the placenta to cause disease in the fetus.
2. This is usually a mild infection, a self-limiting disease with only rare complications in children and adults.
3. Pregnant women infected in the first trimester of women can have a devastating effect on the fetus.
4. In utero fetus may have death or rubella syndrome.
5. The congenital abnormalities are the following:
   1. The cardiovascular system shows patent ductus arteriosus.
   2. Eyes show cataracts and glaucoma.
   3. The central nervous system shows mental retardation and deafness.

Groups requiring the immune status are:

1. Preschool and school-aged children.
2. All females at or just before the childbearing age.
3. All women are to be married.
4. In the case of a married woman, if she is not vaccinated, then she should be vaccinated and avoid becoming pregnant for at least three months because there is a remote possibility that the fetus may be infected.
5. Pregnant women are not positive for rubella immunity. To avoid any infection in fetuses, advise the IgM antibody test. If she is not vaccinated then try to avoid exposure to rubella infection.
6. Healthcare workers should be vaccinated to prevent the spread of infection to pregnant women.

The complication of Rubella infection:

1. If the pregnant woman develops rubella infection in the first trimester, complications are devastating for the fetus.
2.  Complications of birth defects  in a pregnant woman:
   1. Deafness.
   2. Cataracts.
   3. Heart defects.
   4. Mental retardation.
   5. Liver and spleen damage.
3. Rubella syndrome when the following complications are seen:
   1. Encephalitis.
   2. Microcephaly.
   3. Hepatomegaly.
   4. Splenomegaly
   5. Bone defects.
   6. Mental retardation.
   7. Cataract.
   8. Thrombocytopenic purpura.
   9. Cardiovascular defects.
   10. Stillbirth.
4. At least a 20% chance of damage to the fetus if a woman is infected early in pregnancy.
   1. Increased chances of spontaneous abortion and stillbirth.

The outcome of Rubella infection:

1. Utero-infection can result in the death of the fetus.
2. First trimester chances of anomalies = around 25%
3. Second trimester                                     = <1%
4. First month                                              = 50% ±
5. Second month                                         = 25% ±
6. Third month                                            = 10% ±
7. Infected infants shed viruses for up to one year.

Mode of transmission:

1. This disease is spread by contact with an infected person through coughing and sneezing.
2. It spreads through respiratory secretions.

Immunology of Rubella infection:

• There is the formation of antibody IgM and IgG against rubella.
• If IgG and IgM are negative, the patients never suffered from rubella infection and have not been vaccinated.

1. IgM appears in a few days to weeks after the onset of the rubella rash.
   1. IgM disappears in about 6 weeks.
   2. For active disease, advise IgM.
   3. To identify congenital infection, advise IgM.
   4. IgM is necessary to label acute infection.
   5. IgM can not cross the placental barrier. Therefore, the presence of IgM in the neonatal period is diagnostic of congenital rubella syndrome. 
   6. IgM will be positive for at least 6 months in the newborn to confirm the rubella infection.
2. IgG persists at a low level and is detectable for years.
   1. For immune status, advise IgG.
      1. IgG titer of 1:8 or more indicates past infection and future protection from the rubella infection.
      2. Titers of 1:8, 1:16, 1:64, and 1:512 or greater are found in acute and past infections.
      3. To confirm acute infection, then advise IgM on the same serum sample.
   2. IgG can cross the placental barrier and enter into fetal circulation.
3. Acquired infection:
   1. In the case of primary rubella infection, the presence of IgM and IgG antibodies are associated with the appearance of clinical signs and symptoms.
   2. IgM is detectable a few days after the onset of S/S and reach a peak level at 7 to 10 days.
   3. These antibodies persist but decrease in concentration over the next 4 to 5 weeks until these antibodies are not detectable.
   4. IgG remains present and protective indefinitely.
4. Congenital infection:
   1. As IgG can cross the placental barrier, so cannot distinguish in the fetal or maternal IgG antibodies in the neonatal blood.
   2. IgM testing is not valuable as it can not cross the placental barrier.

Diagnostic tests methodology:

1. Latex agglutination.
2. Hemagglutination inhibition (HAI).
3. Passive hemagglutination  (PHA).
4. Enzyme Immunoassay for IgM.
   1. Enzyme immunoassay for IgG.
5. Radioimmunoassay (RIA).
6. Fluorescent immunoassay (FIA).

The normal level of Rubella serology:

Source 1

• The serologic tests are used to determine the following:
  • The immune status of the individual.
  • Diagnose postnatal rubella.
  • Occasionally to support the diagnosis of rubella.
  • IgM antibody disappears within 4 to 5 weeks.
    • IgG antibody remains for life.
• For Diagnosis, EIA is the preferred method, while others are acceptable.

Source 2

Latex agglutination method 

1. This is rapid and convenient.
2. Normal = Negative for IgG and IgM antibodies.
3. IgG positive indicates previous exposure or current immunization.
4. IgM positive indicates current or recent infection.

HAI  (Hemagglutination inhibition method)

1. <1:8 = No immunity to infection.
2. >1:20 = Immunity to rubella infection.
3. The disadvantage is that it detects both IgM and IgG.

ELIZA

1. IgM = >1.1 IU/mL = Indicate  Active infection.
2. IgG = <7 IU/mL = Indicate No immunity to rubella.
3. IgG = >10 IU/mL = Indicate Immunity to rubella.

Semiquantitative immunoassay method 

• • This is an indirect enzyme-labeled immunoabsorbent assay using microwells of a solid phase.

Prevention of the Rubella infection:

1. Vaccination is needed.
   1. A vaccine, as a live virus, is part of MMR.

Questions and answers: