|Year : 2012 | Volume
| Issue : 4 | Page : 269-272
Targeting rubella for elimination
Davendra K Taneja1, Pragya Sharma2
1 Director-Professor, Department of Community Medicine, Maulana Azad Medical College, New Delhi, India
2 Assistant Professor, Department of Community Medicine, Maulana Azad Medical College, New Delhi, India
|Date of Web Publication||24-Jan-2013|
Davendra K Taneja
Director-Professor, Department of Community Medicine, Maulana Azad Medical College, New Delhi - 110 002
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Rubella is an acute, usually mild viral disease. However, when rubella infection occurs just before conception or during the first 8-10 weeks of gestation, it causes multiple fetal defects in up to 90% of cases, known as Congenital Rubella Syndrome (CRS). It may result in fetal wastage, stillbirths and sensorineural hearing deficit up to 20 weeks of gestation. Rubella vaccine (RA 27/3) is highly effective and has resulted in elimination of rubella and CRS from the western hemisphere and several European countries. Review of several studies documents the duration of protection over 10-21 years following one dose of RA27/3 vaccination, and persistent seropositivity in over 95% cases. Studies in India show seronegativity to rubella among adolescent girls to vary from 10% to 36%. Although due to early age of infection resulting in protection in the reproductive age group, incidence of rubella in India is not very high. However, due to severity of CRS coupled with introduction of RCV in private sector and in some of the states which is likely to lead to sub-optimal coverage and resulting higher risk of rubella during pregnancy in the coming decades, it is imperative to adopt the goal of rubella elimination. As in order to control measles, the country has adopted strategy of delivering second dose of measles through measles campaigns covering children 9 months to 10 years of age in 14 states, it is recommended to synergize efforts for elimination of rubella with these campaigns by replacing measles vaccine by MR or MMR vaccine. Other states which are to give second dose of measles through routine immunization will also have to adopt campaign mode in order to eliminate rubella from the country over 10-20 years. Subsequently, measles vaccine can be replaced by MR or MMR vaccine in the national schedule.
Keywords: Burden, Elimination, Rubella, Vaccination
|How to cite this article:|
Taneja DK, Sharma P. Targeting rubella for elimination. Indian J Public Health 2012;56:269-72
| Introduction|| |
Rubella is an acute, usually mild, viral disease traditionally affecting susceptible children and young adults worldwide. From just before conception and during the first 8-10 weeks of gestation, rubella infection may cause multiple fetal defects in up to 90% of cases, known as congenital rubella syndrome (CRS). It may result in fetal wastage, stillbirth and sensorineural hearing deficit up to 20 weeks of gestation.
| Global Burden of Disease|| |
Before the introduction of rubella vaccine, the incidence of CRS varied from 0.1 to 0.2/1000 live births during endemic periods and from 0.8 to 4/1000 live births during rubella epidemics. It has been estimated that in 1996, approximately 22,000 children with CRS were born in Africa, 46,000 in South-East Asia, and 12,634 in the Western Pacific region. 
| Rubella Vaccines|| |
Most of the licensed rubella vaccines are based on the live attenuated RA 27/3 strain which is propagated in human diploid cells. Commonly used recombinant vaccines (RCVs) are combinations like Measles Rubella (MR), Measles Mumps Rubella (MMR), or Measles Mumps Rubella Varicella (MMRV). The immune response to rubella antigen is not affected by the other components. 
| Schedules|| |
In most countries, rubella vaccine is given as MR or MMR, and the age of administration follows the schedule for measles, i.e., the first dose is usually given at 9 months or 12-15 months and a second dose at 15-18 months or 4-6 years. 
High response to single dose of rubella vaccine (≥95%) and the long-term persistence of protection in vaccines do not support a routine requirement for a second dose of rubella vaccine. However, based on the indications for a second dose of measles-containing and mumps-containing vaccines, a second dose of MR or of MMR is now offered in most countries. 
RCV is normally administered as a subcutaneous injection; however, it may also be given intramuscularly.
| Efficacy and Effectiveness|| |
The effectiveness of the RA 27/3 vaccine has been demonstrated by the elimination of rubella and CRS from the western hemisphere and by the several European countries that have achieved and maintained high vaccination coverage with vaccines containing RA 27/3. In outbreak situations, the effectiveness of different rubella vaccines has been estimated to be 90-100%. Protection was attained 2-3 weeks after immunization. 
| Duration of vaccine-induced immunity and risk of reinfection|| |
Vaccine-induced immunity is generally assumed to be lifelong, although rubella antibodies may fall below detectable levels. A study conducted in Taiwan reported the mean annual antibody decay rate as −0.77 IU/ml in women of childbearing age who were vaccinated with RA 27/3 at junior high school age.  However, reviews of several studies document the duration of protection over 10-21 years following one RA 27/3 vaccination, and persistent seropositivity over 95%. Reinfection is a rare occurrence, and in the event of rubella reinfection occurring during the first 12 weeks of pregnancy in a previously vaccinated woman, the risk of congenital infection is likely to be low. 
| Vaccine Safety and Adverse Reactions|| |
Adverse reactions are generally mild among children. Common adverse reactions include pain, redness, and induration at the site of injection. Low-grade fever and rash, irritability, lymphadenopathy, myalgia and paresthesia have been commonly reported. Joint-related symptoms tend to be rare in children (occurring in 0-3%) and in men. However, in susceptible adult women, arthralgias have been reported in 25%, and frank arthritis in 12%. These reactions usually occur 7-21 days postvaccination and last from a few days to 2 weeks. Anaphylaxis is rare after RA 27/3 vaccine. 
| Epidemiological Impact of Rubella Vaccination|| |
- Introduction of vaccine among children: With the introduction of vaccine, the average age of those infected increases. However, if vaccination coverage is high, age-specific incidence decreases in all age groups. On the other hand, when vaccine coverage is low (e.g., in a suboptimal childhood-only immunization program or when rubella vaccination is offered only in the private sector), the circulation of the virus may be decreased enough so that those who would normally be infected as children will remain susceptible until they reach adolescence and adulthood. In such settings, an increase in CRS cases may be predicted from mathematical models. 
- Immunization is targeted only at adolescent girls or women of childbearing age: The epidemiology of rubella and circulation of rubella virus remain largely unaffected as most infections occur before the age at immunization. With such an approach, the incidence of CRS declines linearly with increasing levels of coverage. However, elimination of CRS is unlikely to be achieved with this strategy alone, as it would require every susceptible woman to be effectively immunized.
| Goals and Strategies for Rubella Prevention|| |
Primary goal: To prevent congenital rubella infection, including CRS.
| Approaches to the use of RCVs|| |
- Immunizing adolescent girls or women of child-bearing age: Vaccinating only adolescent girls and women of childbearing age results in a decline in CRS that is proportional to the level of coverage achieved.
- Introduction of RCV into routine childhood immunization schedule and combined with the vaccination of older age groups who are susceptible to rubella: More extensive the implementation of vaccination strategies, the shorter will be the time frame for eliminating rubella and CRS. Thus, when vaccination coverage is high, e.g., more than 85% and only young children (such as those aged 1-4 years) are immunized, rubella and CRS will be eliminated in approximately 20-30 years. It will be eliminated in approximately 10-20 years when vaccination at high coverage is provided to young children and adolescents, i.e., children aged 1-14 years, and within 10 years when vaccination at high coverage is provided to young children, adolescents, and adults, i.e., people aged 1-39 years of age. 
| Cost Effectiveness|| |
In high-income and middle-income countries, caring for CRS cases is costly, and rubella vaccination has been found to be cost-effective. However, no such studies have been conducted in low-income countries in Africa and Asia. 
| WHO Position on Rubella Vaccines|| |
WHO recommends that countries take the opportunity offered by accelerated measles control and elimination activities to introduce RCVs. All countries providing two doses of measles vaccine using routine immunization or SIAs, or both, should consider including RCVs in their immunization program. Because rubella is not as highly infectious as measles and because the effectiveness of one dose of an RCV is ≥95% even at age 9 months, only one dose of rubella vaccine is required to achieve rubella elimination if high coverage is achieved. However, when combined with measles vaccination, it may be easier to implement a second dose of RCVs using the same combined MR vaccine or MMR vaccine for both doses. 
| Situation in India|| |
Susceptibility to rubella: There is a considerable variation in the prevalence of rubella antibodies among adolescent girls and women of child-bearing age, depending on the socioeconomic strata and selection of study group.
In a study conducted in North India among girls aged 9-12 years to 15-18 years, seronegativity to rubella has been reported from 10 to 36%, ,,, whereas seronegativity among women of child-bearing age group has been reported to be 10-15%.  However, these women were referred for rubella screening either due to bad obstetric history or possible infection during pregnancy or immunity to rubella. Therefore, seronegativity in this study is likely to be underreported than general population.
In a study conducted in five districts of Tamilnadu among subjects aged 1-5 years and 10-16 years to assess susceptibility to Rubella, overall, 48.3% of the study population was found to be seronegative.  Another study from South India, Tamilnadu, conducted among female hospital staff of three eye hospitals, aged 18-40 years reported seronegativity to rubella in the range of 11.7-20.8%. 
Seroconversion studies: In India, >95% of children seroconverted after being vaccinated at 9 months of age. There was no difference in seroconversion rates when rubella vaccine was given at 9 months or 15 months of age. 
Immunization against rubella: Rubella vaccine is available in private sector in the country and is commonly administered as MMR vaccine at 15 months of age. Four states/UTs (Delhi, Goa, Puducherry, and Sikkim) are using MMR vaccine for giving second dose of measles in their routine immunization program.
| Recommendations|| |
Although due to early age of infection resulting in protection in the reproductive age group, incidence of rubella in India is not high. However, severity of CRS coupled with introduction of RCV in private sector and in some of the states, which is likely to lead to sub-optimal coverage and resulting higher risk of rubella during pregnancy in the coming decades, makes it imperative to introduce rubella vaccine in the National Immunization Schedule. As India has adopted the two-dose strategy for measles control, it will be tremendous operational saving to synergize with it efforts aimed at rubella elimination.
It is recommended that the country adopts goal and strategy for rubella elimination in about 10-20 years through immunization of children and adolescents, i.e., children 1-14 years of age.
For operational feasibility and higher coverage, rubella vaccine can be administered along with measles vaccine in 14 states of India by replacing measles vaccine with MR or MMR vaccine where measles follow-up campaigns for children aged 9 months to 10 years are being carried out. Simultaneously, this strategy will have to be implemented in other states, which are implementing measles control strategy by giving second dose of measles vaccine as part of routine immunization. To achieve target for elimination of CRS in next 10-20 years, single dose of rubella vaccine can be incorporated in the National Immunization schedule replacing measles vaccine with MR or MMR in the subsequent birth cohorts.
| References|| |
|1.||Rubella vaccines: WHO position paper. Wkly Epidemiol Rec 2011;86:301-16. |
|2.||Lin CC, Yang CY, Shih YL, Huang YY, Yang TH, Liang JY, et al. Persistence and titer changes of rubella virus antibodies in primiparous women who had been vaccinated with strain RA 27/3 in junior high school. Clin Vaccine Immunol 2012;19:1-4. |
|3.||Yadav S, Wadhwa V, Chakarvarti A. Prevalence of rubella antibody in school going girls. Indian Pediatr 2001;38:280-3. |
|4.||Sharma H, Chowdhari S, Raina TR, Bhardwaj S, Namjoshi G, Parekh S. Sero-surveillance to assess immunity to rubella and assessment of immunogenicity and safety of a single dose of rubella vaccine in school girls. Indian J Community Med 2010;35:134-7. |
|5.||Singla N, Jindal N, Aggarwal A. The seroepidemiology of Rubella in Amritsar (Punjab). Indian J Med Microbiol 2004;22:61-3. |
|6.||Rustgi R, Deka D, Singh S. Rubella serology in Indian adolescent girls and its relation to socio-economic status. J Obstet Gynecol India 2005;55:167-9. |
|7.||Gandhoke I, Aggarwal R, Lal S, Khare S. Seroprevalence and incidence of rubella in and around Delhi (1988-2002). Indian J Med Microbiol 2005;23:164-7. |
|8.||Ramamurty N, Murugan S, Raja D, Elango V, Mohana, Dhanagaran D. Serosurvey of rubella in five blocks of Tamil Nadu. Indian J Med Res 2006;123:51-4. |
|9.||Vijayalakshmi P, Anuradha R, Prakash K, Narendran K, Ravindran M, Prajna L, et al. Rubella serosurveys at three Aravind Eye Hospitals in Tamil Nadu, India. Bull World Health Organ 2004;82:259-64. |
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