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Background

This is a mild viral illness caused by the rubella virus. It is associated with a mild fever, rash, and aches in the joint. The importance in correctly making the diagnosis is the prevention of disease in preganant women. There are significant sequalae for the unborn child as outlined below.

OUTLINE

Epidemiology  
Disease Associations  
Prognosis  
Treatment  
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EPIDEMIOLOGY CHARACTERIZATION
EPIDEMIOLOGIC ASSOCIATIONS  

Global distribution of rubella virus genotypes.

Zheng DP, Frey TK, Icenogle J, Katow S, Abernathy ES, Song KJ, Xu WB, Yarulin V, Desjatskova RG, Aboudy Y, Enders G, Croxson M.

Georgia State University, Atlanta, Georgia 30303, USA.

Emerg Infect Dis. 2003 Dec;9(12):1523-30. Abstract quote  

Phylogenetic analysis of a collection of 103 E1 gene sequences from rubella viruses isolated from 17 countries from 1961 to 2000 confirmed the existence of at least two genotypes. Rubella genotype I (RGI) isolates, predominant in Europe, Japan, and the Western Hemisphere, segregated into discrete subgenotypes; international subgenotypes present in the 1960s and 1970s were replaced by geographically restricted subgenotypes after approximately 1980.

Recently, active subgenotypes include one in the United States and Latin America, one in China, and a third that apparently originated in Asia and spread to Europe and North America, starting in 1997, indicating the recent emergence of an international subgenotype.

A virus that potentially arose as a recombinant between two RGI subgenotypes was discovered. Rubella genotype II (RGII) showed greater genetic diversity than did RGI and may actually consist of multiple genotypes. RGII viruses were limited to Asia and Europe; RGI viruses were also present in most of the countries where RGII viruses were isolated.

 

DISEASE ASSOCIATIONS CHARACTERIZATION
ATOPIC DERMATITIS  

Atopic dermatitis is increased following vaccination for measles, mumps and rubella or measles infection.

Olesen AB, Juul S, Thestrup-Pedersen K.

Department of Dermatology, University Hospital of Aarhus, Denmark.
Acta Derm Venereol. 2003;83(6):445-50. Abstract quote  

The prevalence of atopic dermatitis increased markedly in the period 1960s to the 1990s. Earlier findings indicate that infections acquired in early life enhance or suppress the expression of atopic disease as a result of a change in immune reactivity. Our objectives were to examine the association between measles, mumps and rubella vaccination, measles infection and the risk of atopic dermatitis. A random sample of 9,744 children were followed up from birth to 3-15 years.

Their parents responded to a questionnaire including highly structured questions on atopic dermatitis, measles, mumps and rubella vaccination and measles infection. Information on parental educational level was obtained from Statistics Denmark. The cumulative incidence of atopic dermatitis at age 14 was 19.7%. The confounder adjusted incidence ratio of atopic dermatitis among measles, mumps and rubella vaccinated children versus children not subjected to measles, mumps and rubella vaccination and measles infection was 1.86 (95% CI 1.25-2.79); the incidence ratio for measles-infected children was similar. The incidence of atopic dermatitis increased after measles, mumps and rubella vaccination and measles infection, which is surprising in view of the hygiene hypothesis.

We suggest further study of the possible short-term and long-term effects of virus and bacteria on the immune responses and expression of atopic disease.
AUTISM  

Measles-mumps-rubella vaccine and the development of autism.

Miller E.

Immunisation Division, Public Health Laboratory Service, 61 Colindale Avenue, London NW9 5EQ, UK. .
Semin Pediatr Infect Dis. 2003 Jul;14(3):199-206. Abstract quote  


The measles-mumps-rubella (MMR) vaccine has been postulated to cause a form of autism characterized by regression and bowel symptoms, and onset occurring shortly after vaccination.

It is also claimed that, as a result, there has been a dramatic increase in autism prevalence. These hypotheses have now been tested in a number of epidemiologic studies that are reviewed in this article. None has found any evidence of the existence of a phenotypically distinct form of autism in children who received the MMR vaccine or of a clustering of onset symptoms in children who are autistic after receiving the MMR vaccine.

There is no proof that the overall risk of autism is higher in children who were vaccinated with MMR or of an increase in autism prevalence associated with the use of the MMR vaccine. No epidemiologic evidence suggests an association between MMR vaccination and autism. Moreover, epidemiologic evidence against such an association is compelling.

PREGNANCY  

Prevalence of birth defects and rubella infection in pregnant women in Gansu, west China. A survey.

Cheng N, Bai Y, Hu X, Pei H, Li Y, Zhang W, Fan X, Zhang P, Zhou X, Chen Z, Li C, He P, He H.

Central Laboratory of Cellular and Molecular Biology, Department of Epidemiology, Lanzhou Medical College, Women and Children's Hospital of Gansu, Institute of Science Research, Lanzhou, People's Republic of China.
J Reprod Med. 2003 Nov;48(11):869-74. Abstract quote  

OBJECTIVE: To determine the incidence, disease types, sequence of birth defects and prevalence of IgG and IgM in rubella infection in prepregnancy and pregnancy within 3 months in Gansu, People's Republic of China, and to determine a baseline of birth defects for an intervention project on birth defects in Gansu.

STUDY DESIGN: Liveborn and stillborn infants from January 1, 2001, to January 1, 2002, and 518 prepregnant and 373 pregnant women in 3 months in 4 counties, including 42 communities selected random by stratification cluster sampling for a survey on the economic and geographic features in the province in October 2001 were investigated. Every infant born in the study period was surveyed. The types of birth defects were classed by standard diagnostic codes (ICD-9). Five-milliliter blood samples were obtained from every prepregnant and pregnant women. Rubella IgG and IgM were measured by enzyme-linked immunosorbent assay.

RESULTS: The overall number of birth defects in Gansu was 102 (16.35%). The incidence of birth defects by sex was 62 males (18.55%) and 40 females (13.9%). The types of birth defects were neural tube defect, 44 cases (7.07%); limb defects, 13 (2.09%); cleft lip and palate, 5 (0.8%); and Down syndrome, 3 (0.48%). Low birth weight occurred in 31 cases (4.98%). The seasonal incidence birth defects was spring, 24 cases (23.52%); summer, 31 (30.39%); autumn, 26 (25.49%); and winter, 21 (20.59%). There were significant differences between 4 counties. The death rate from birth defects was 48 cases (47.06%). The positive rates of IgM and IgG of rubella infection of prepregnant women were, respectively, 5.02% and 83.78%; in pregnant women they were, respectively, 2.41% and 86.33%. The seropositive rate of rubella infection of prepregnancy was 88.80%; that of pregnancy was 88.74%.

CONCLUSION: The rate of rubella infection in prepregnant and pregnant women within 3 months in Gansu was one of the highest in the People's Republic of China. The rate of birth defects in Gansu was one of much higher than in the People's Republic of China as a whole.

PROGNOSIS CHARACTERIZATION
Damage to unborn fetus (multiple defects common) 9 out of 10 pregnancies (in the first 8 to 10 weeks)
Damage to unborn fetus 1 in 5 to 10 (between 10 and 16 weeks)
After 16 weeks damage is rare
Bleeding disorders 1 in 3000
Encephalitis 1 in 6000

TREATMENT CHARACTERIZATION
GENERAL  
VACCINE  
MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis.

Vestergaard M, Hviid A, Madsen KM, Wohlfahrt J, Thorsen P, Schendel D, Melbye M, Olsen J.

The Danish Epidemiology Science Centre, Department of Epidemiology and Social Medicine, Aarhus University, Aarhus, Denmark.
JAMA. 2004 Jul 21;292(3):351-7. Abstract quote  

CONTEXT: The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination.

OBJECTIVES: To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination.

DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries.

MAIN OUTCOME MEASURES: Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy.

RESULTS: A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure.

CONCLUSIONS: MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology.

Measles, mumps, rubella vaccine (Priorix; GSK-MMR): a review of its use in the prevention of measles, mumps and rubella.

Wellington K, Goa KL.

Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 2003;63(19):2107-26. Abstract quote  

GSK-MMR (Priorix) is a trivalent live attenuated measles, mumps and rubella (MMR) vaccine which contains the Schwarz measles, the RIT 4385 mumps (derived from the Jeryl Lynn mumps strain) and the Wistar RA 27/3 rubella strains. GSK-MMR as a primary vaccination demonstrated high immunogenicity in clinical trials in >7500 infants aged 9-27 months, and was as immunogenic as Merck-MMR (MMR II). However, antimumps seroconversion rates and geometric mean titres (GMTs) were significantly higher in infants receiving GSK-MMR compared with Berna-MMR (Triviraten trade mark ) recipients. Coadministration of GSK-MMR with a varicella vaccine (Varilrix; GSK-MMR/V) did not significantly affect the immunogenicity of GSK-MMR.

A persistent immune response to GSK-MMR has been demonstrated in follow-up data from several randomised trials. GMTs for measles, mumps and rubella antibodies remained high in GSK-MMR recipients 1-2 years post-vaccination and were similar to those in Merck-MMR recipients. The immunogenicity of GSK-MMR was high, and similar to that of Merck-MMR, when used as a second dose in children aged 4-6 or 11-12 years who had received a primary vaccination with Merck-MMR in their second year of life. Although there are no protective efficacy data concerning the GSK-MMR vaccine to date, the rubella Wistar RA 27/3 rubella and Schwarz measles strains have well established protective efficacy; the new RIT 4385 mumps strain is expected to afford similar protection from mumps to that achieved with mumps vaccines that contain the Jeryl Lynn mumps strain (e.g. Merck-MMR). GSK-MMR was well tolerated as a primary or secondary vaccination, and in most clinical studies comparing GSK-MMR with Merck-MMR as a primary vaccination in infants, GSK-MMR was associated with significantly fewer local adverse events (e.g. pain, swelling and redness). The incidence of local adverse events with GSK-MMR, GSK-MMR/V or Berna-MMR was similar. GSK-MMR and Merck-MMR were associated with similar rates of fever, rash and parotid gland swelling, but Berna-MMR was associated with a lower incidence of fever. In conclusion, GSK-MMR is a highly immunogenic MMR vaccine with good tolerability.

In clinical trials, the immunogenicity of GSK-MMR was similar to that of Merck-MMR, and the mumps component was more effective at eliciting seroprotection than that of Berna-MMR. Furthermore, GSK-MMR causes fewer injection-site adverse events than Merck-MMR. As such, GSK-MMR is an attractive alternative for immunisation against measles, mumps and rubella.

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Last Updated 7/28/2004

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