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Test ID: MMRV    
MMRV Immune Status Profile, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Determination of immune status of individuals to measles, mumps, rubella, and varicella-zoster viruses (VZV)

 

Documentation of previous infection with measles, mumps, rubella, or VZV in an individual without a previous record of immunization to these viruses

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Measles:

The measles virus is a member of the Paramyxoviridae family of viruses, which include parainfluenza virus serotypes 1-4, mumps, respiratory syncytial virus (RSV), and metapneumovirus. The measles virus is among the most highly contagious infectious diseases among unvaccinated individuals and is transmitted through direct contact with aerosolized droplets or other respiratory secretions from infected individuals. Measles has an incubation period of approximately 8 to 12 days, which is followed by a prodromal phase of high fever, cough, coryza, conjunctivitis, and malaise. Koplik spots may also be apparent on the buccal mucosa and can last for 12 to 72 hours.(1) Following this phase, a maculopapular, erythematous rash develops beginning behind the ears and on the forehead and spreading centrifugally to involve the trunk and extremities.

 

Immunocompromised individuals, pregnant women, and those with nutritional deficiencies are particularly at risk for serious complications following measles infection, which include pneumonia and central nervous system involvement.(1)

 

Following implementation of the national measles vaccination program in 1963, the incidence of measles infection has fallen to <0.5 cases per 1,000,000 population and the virus is no longer considered endemic in the United States. Measles outbreaks continue to occur in the United States due to exposure of nonimmune individuals or those with waning immunity to infected travelers. The measles outbreak in 2011 throughout Western Europe emphasizes the persistence of the virus in the worldwide population and the continued need for national vaccination programs.(2)

 

The diagnosis of measles infection is often based on clinical presentation alone. Screening for IgG-class antibodies to measles virus will aid in identifying nonimmune individuals.

 

Mumps:

The mumps virus is a member of the Paramyxoviridae family of viruses, which include parainfluenza virus serotypes 1-4, measles, RSV, and metapneumovirus. Mumps is highly infectious among unvaccinated individuals and is typically transmitted through inhalation of infected respiratory droplets or secretions. Following an approximately 2-week incubation period, symptom onset is typically acute with a prodrome of low-grade fever, headache, and malaise.(3,4) Painful enlargement of the salivary glands, the hallmark of mumps, occurs in approximately 60% to 70% of infections and in 95% of patients with symptoms. Testicular pain (orchitis) occurs in approximately 15% to 30% of postpubertal men and abdominal pain (oophoritis) is found in 5% of postpubertal women.(3) Other complications include mumps-associated pancreatitis (<5% of cases) and central nervous system disease (meningitis <10% and encephalitis <1%).

 

Widespread routine immunization of infants with attenuated mumps virus has dramatically decreased the number of reported mumps cases in the United States. However, outbreaks continue to occur, indicating persistence of the virus in the general population.

 

Laboratory diagnosis of mumps is typically accomplished by detection of IgM- and IgG-class antibodies to the mumps virus. However, due to the widespread mumps vaccination program, in clinically suspected cases of acute mumps infection, serologic testing should be supplemented with virus isolation in culture or detection of viral nucleic acid by PCR in throat, saliva, or urine specimens.

 

Rubella:

Rubella (German or 3-day measles) is a member of the togavirus family and humans remain the only natural host for this virus. Transmission is typically through inhalation of infectious aerosolized respiratory droplets and the incubation period following exposure can range from 12 to 23 days.(5) Infection is generally mild and self-limited, and is characterized by a maculopapular rash beginning on the face and spreading to the trunk and extremities, fever, malaise, and lymphadenopathy.(6)

 

Primary in utero rubella infections can lead to severe sequelae for the fetus, particularly if infection occurs within the first 4 months of gestation. Congenital rubella syndrome is often associated with hearing loss, and cardiovascular and ocular defects.(7)

 

The US 2-dose measles, mumps, and rubella (MMR) vaccination program, which calls for vaccination of all children, leads to seroconversion in 95% of children following the first dose.(5) A total of 4 cases of rubella were reported to the CDC in 2011 without any cases of congenital rubella syndrome.(8) Due to the success of the national vaccination program, rubella is no longer considered endemic in the United States (cdc.gov/rubella). Immunity may however wane with age as approximately 80% to 90% of adults will show serologic evidence of immunity to rubella.

 

Varicella-Zoster Virus (VZV):

VZV, a herpes virus, causes 2 distinct exanthematous (rash-associated) diseases: chickenpox (varicella) and shingles (herpes zoster). Chickenpox is a highly contagious though typically benign disease usually contracted during childhood. Chickenpox is characterized by a dermal vesiculopustular rash that develops in successive crops approximately 10 to 21 days following exposure.(9) Although primary infection with VZV results in immunity and protection from subsequent infection, VZV remains latent within sensory dorsal root ganglia and upon reactivation, manifests as herpes zoster or shingles. During reactivation, the virus migrates along neural pathways to the skin, producing a unilateral rash, usually limited to a single dermatome. Shingles is an extremely painful condition typically occurring in older, nonimmune adults or those with waning immunity to VZV and in patients with impaired cellular immunity.

 

Individuals at risk for severe complications following primary VZV infection include pregnant women, in whom the virus may spread through the placenta to the fetus, causing congenital disease in the infant. Additionally, immunosuppressed patients are at risk for developing severe VZV-related complications, which include cutaneous disseminated disease and visceral organ involvement.

 

Serologic screening for IgG-class antibodies to VZV will aid in identifying nonimmune individuals.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Measles, Mumps and Varicella

Vaccinated: Positive (> or =1.1 AI)

Unvaccinated: Negative (< or =0.8 AI)

 

Rubella

Vaccinated: Positive (> or =1.0 AI)

Unvaccinated: Negative (< or =0.7 AI)

Interpretation Provides information to assist in interpretation of the test results

Positive Measles, Mumps, Varicella-Zoster Viruses (VZV): Antibody Index Value > or =1.1  

Positive Rubella: Antibody Index Value > or =1.0

 

The reported Antibody Index (AI) value is for reference only. This is a qualitative test and the numeric value of the AI is not indicative of the amount of antibody present. AI values above the manufacturer recommended cutoff for this assay indicate that specific antibodies were detected, suggesting prior exposure or vaccination.

 

The presence of detectable IgG-class antibodies to these viruses indicates prior exposure through infection or immunization. Individuals testing positive for IgG-class antibodies to measles, mumps, rubella, or VZV are considered immune.

 

Equivocal Measles, Mumps, VZV: Antibody Index Value 0.9-1.0

Equivocal Rubella: Antibody Index Value 0.8-0.9

 

Submit an additional sample for testing in 10 to 14 days to demonstrate IgG seroconversion if recently vaccinated or if otherwise clinically indicated. 

 

Negative Measles, Mumps, VZV: Antibody Index Value < or =0.8

Negative Rubella: Antibody Index Value < or =0.7

 

The absence of detectable IgG-class antibodies to measles, mumps, rubella, or VZV suggests no prior exposure to these viruses or the lack of a specific immune response to immunization.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

IgG-class antibodies to measles, mumps, rubella, or varicella-zoster virus may be present in serum specimens from individuals who have received blood products within the past several months, but have not been immunized or experienced past infection with this virus.

 

Specimens drawn early during the acute phase of infection or shortly (1-2 weeks) following vaccination may be negative for IgG-class antibodies.

Supportive Data

To evaluate the accuracy of the BioPlex MMRV assay, 500 prospective serum samples submitted to the laboratory for routine MMRV testing by EIA were also analyzed by the BioPlex assay within a 24-hour period. Routine testing for measles and varicella-zoster IgG was performed by Diamedix EIA (Diamedix, Miami, FL), while routine analysis of mumps and rubella IgG was completed using the SeraQuest EIA assays (Quest Int., Doral, FL). Samples that had discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. Further discrepancies were evaluated by a third method. Samples showing discordant results for measles and varicella IgG were tested using SeraQuest EIAs, while discrepant samples for mumps and rubella IgG were tested by ELFA (VIDAS, bioMerieux, Inc.). Results are summarized in the tables below:

 

1. Measles IgG

 

Diamedix Measles IgG EIA

BioPlex Measles IgG

 

Positive

Negative

Equivocal

Positive

420

1(a)

0

Negative

10(b)

27

17

Equivocal

14

0

11

(a) This sample tested negative by the SeraQuest Measles IgG EIA

(b) All 10 samples tested positive by the SeraQuest Measles IgG EIA

Sensitivity: 94.6% (420/444); 95% Confidence Intervals (95% CI): 92.1% to 96.4%

Specificity: 96.4% (27/28); 95% CI: 80.8% to 100.0%

Overall Percent Agreement: 91.6% (458/500); 95% CI: 88.8% to 93.8%

 

2. Mumps IgG

 

SeraQuest Mumps IgG EIA

BioPlex Mumps IgG

 

Positive

Negative

Equivocal

Positive

412

4(a)

8

Negative

3(b)

48

3

Equivocal

5

6

11

(a) All 4 of these samples tested positive by VIDAS Mumps IgG ELFA

(b) One of these 3 samples tested negative by the VIDAS Mumps IgG ELFA

Sensitivity: 98.1% (412/420); 95% Confidence Intervals (CI): 96.2% to 99.1%

Specificity: 82.8% (48/58); 95% CI: 70.9% to 90.6%

Overall Percent Agreement: 94.2% (471/500); 95% CI: 91.8% to 96.0%

 

3. Rubella IgG

 

SeraQuest Rubella IgG EIA

BioPlex Rubella IgG

 

Positive

Negative

Equivocal

Positive

446

0

0

Negative

7(a)

23

4

Equivocal

17

0

3

(a) 6/7 samples tested as equivocal by the VIDAS Rubella IgG ELFA

Sensitivity: 94% (446/470); 95% Confidence Interval (95% CI): 92.5% to 96.6%

Specificity: 100% (23/23); 95% CI: 83.1% to 100%

Overall Percent Agreement: 94.4% (472/500); 95% CI: 92.0% to 96.1%

 

4. Varicella-Zoster IgG

 

Diamedix VZV IgG EIA

BioPlex VZV IgG

 

Positive

Negative

Equivocal

Positive

436

0

0

Negative

18(a)

22

4

Equivocal

19

0

1

(a) All 18 samples tested positive by the SeraQuest VZV IgG EIA

Sensitivity: 92.2% (436/473); 95% Confidence Interval (95% CI): 89.4% to 94.3%

Specificity: 100.0 (22/22); 95% CI: 82.5% to 100.0%

Overall Percent Agreement: 91.8% (459/500); 95% CI: 89.0% to 93.9%

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Perry RT, Halsey NA: The clinical significance of measles-a review. J Infect Diseases 2004;189(Supp 1):S4-S16

2. Morbidity and Mortality Weekly Report: Increased transmission and outbreaks of measles-European Region, 2011. 2011;60(47):1605-1610

3. Hviid A, Rubin S, Muhlemann K: Mumps. Lancet 2008 Mar;371(9616):932-944

4. Hodinka RL, Moshal KL: Childhood Infections. In Essentials of Diagnostic Virology. Edited by GA Storch. Churchill Livingstone, New York, 2000, pp 168-178

5. American Academy of Pediatrics. Rubella. In Red Book. 2012 Report of the Committee on Infectious Diseases. Edited by LK Pickering. Elk Grove Village, IL, 2012

6. Best JM: Rubella. Semin Fetal Neonatal Med 2007;12(3):182

7. Duszak RS: Congenital rubella syndrome-major review. Optometry 2009:80(1):36

8. Morbidity and Mortality Weekly Report: Notifiable diseases and mortality tables. 2012:61(34):466-479

9. Yankowitz J, Grose C: Congenital Infections. In Essentials of Diagnostic Virology. Edited by GA Storch. Churchill Livingstone, New York, 2000, pp 187-201