Rubella vaccine

Abstract

Rubella is a contagious viral disease, which mainly affects the fetus, if the mother is infected in the 1st trimester of her pregnancy. All adolescent girls (aged 11 to 19 y) and women of childbearing age are at risk of developing rubella. This disease is mild and self-limiting, and incubation period is 2–3 weeks. Humans are the only hosts for rubella. Rubella infection during pregnancy may lead to abortions, stillbirth or congenital deformities (birth defects). Moreover it is surprising to know that over 200,000 babies are born with birth defects because of Rubella infection during pregnancy in the Indian sub-continent. The risk of fetal infection is highest in first trimester; the infection rate declines between 12–28 weeks, suggesting that the placenta may prevent transfer of virus but not completely. The incidence of defects is inversely related to the time of maternal infection. Rubella outbreaks have been reported from many countries in South East Asian region with congenital rubella syndrome (CRS) due to maternal rubella being on the increase in many countries. In India, although the endemicity of rubella is established, the majority of cases remain undiagnosed, being subclinical or clinically mild. Consequently, in spite of evidence of CRS in all States of India, no distinct policy has been envisaged for assessing the burden of rubella, and no control measures against this silent crippling disease are in place. The European Regional Committee of the World Health Organization has adopted the goals of “Elimination of CRS” in the Health for All programs. There is no treatment for rubella. Vaccination is the only way to prevent all these complications.

Keywords: :

• congenital deformities
• fetus
• rubella
• vaccine
• viral disease

Rubella is a contagious viral disease, which mainly affects the fetus. Rubella affects the fetus if the mother is infected during the first trimester of her pregnancy. All girls aged 11–19 y and women of childbearing age are at risk of developing rubella. Rubella spreads through air by coughing, sneezing, or simply talking. The causative agent of rubella is a single-stranded RNA of positive polarity - the sole member of the Rubivirus genus within the Togaviridae family. The rubella virus genome has approximately 10,000 nucleotides and encodes five protein products including the virion protein, capsid protein and envelope glycoproteins E1 and E2. It multiplies slowly in primary cell structure, in some continuous cell lines, and in most cell systems without cytopathic effects.¹ The common mode of transmission is from person to person by tiny droplets in the air that are breathed out. Second is mother-to-child transmission through placental transfer. This mild, self-limiting, viral disease can last 1–5 d.² Incubation period is 2–3 weeks. Humans are the only hosts for rubella.

It has been observed that around 40–45% of women in the childbearing age are susceptible to rubella. Rubella infection during pregnancy may lead to abortions, stillbirth or congenital deformities (birth defects). Moreover it is surprising to know that over 2 lakh babies are born with birth defects because of rubella infection during pregnancy in the Indian sub-continent.³ These birth defects include Deafness (92%), Cataract (56%), Congenital heart defects (65%), Behavior disorders (32%), Neurological deficit residual (26%), Hearing and visual defect (19%), Diabetes mellitus (1%), and mental retardation in the newborns. Such children become social and economic burden for parents.³

The hallmark of fetal infection is its chronicity, i.e., persistence throughout fetal life and after birth. Once the fetus is infected, the virus persists typically throughout the gestation and several months post-natally. Pharyngeal shedding of virus is more common, prolonged and intense during the early months of delivery. The disease is rare before 1 y of age. The frequency rises slowly at 1–4 y and peaks at around 20–24 y. The risk of fetal infection is highest in first trimester; the infection rate declines between 12–28 weeks, suggesting that the placenta may prevent transfer of virus but not completely. The incidence of defects is inversely related to the time of maternal infection.⁴ This premise has arisen from two large studies by Miller et al. and Chardock-Watson et al. In the last month of pregnancy, an increase in the rate of fetal infection is seen, which indicates an ineffective placental barrier during that time. Pakhau et al. has reported an overall incidence of defects to be 23% at 2 y of age.⁴

The Rubella virus interferes with the development of organs in the fetus. Therefore, depending on the gestation period and the organs developing during that time, the type and the chances of deformities developing in the child varies. The risk of deformities developing is as follows:

Time of maternal infection Result ³

1–2 weeks Harmless

3–11 weeks 100% infected fetus

Twelve weeks 80% infected fetus

13–14 weeks 54% infected fetus

15–16 weeks 35% infected fetus

23–26 weeks 25% infected fetus

Since 1941, rubella has been known to cause congenital malformations in children. Before vaccination, rubella had a worldwide distribution and produced major epidemics at 6- to 9-y intervals. After introduction of the vaccine, the incidence of rubella was reduced to a minimum in developed countries. However, in developing countries without vaccination, epidemiology of rubella remains the same. Rubella causes damage to an unborn child in about 9 out of 10 cases.⁵

Rubella outbreaks have been reported from many countries in South East Asian region with CRS due to maternal rubella being on the increase in many countries. In India, although the endemicity of rubella is established, because most cases are subclinical or clinically mild, the majority of cases remain undiagnosed. Consequently, in spite of evidence of CRS in all States of India, no distinct policy has been envisaged for assessing the burden of rubella and no control measures against this silent crippling disease are in place.⁴

After the devastating pandemic of rubella between 1962 and 1965, the US licensed the use of rubella vaccine in 1969, which resulted in a 99% reduction of cases.⁶ The European Regional Committee of the World Health Organization has adopted the goals of “Elimination of Congenital Rubella Syndrome (CRS)” in the Health for All programs.⁷ It is essential that when immunization against rubella is instituted, more than 80% coverage is achieved in order to assure herd immunity. Haphazard use of rubella vaccine (monovalent or as a constituent of MMR) in young children through public health measures with suboptimal coverage of the target population may be counter-productive, since it may shift the epidemiology of rubella to the older age groups with more clinical cases occurring in young adults, leading to a paradoxical increase in the number of CRS cases. Direct evidence from some Latin American countries and Greece also corroborates this concern. There is a paucity of reliable data on the occurrence of CRS in India. Other developing countries have incidence rates of 0.6–4.1 per 1000 live births. WHO estimates that 100,000 cases of CRS occur in developing countries. Cost-benefit studies in countries with routine vaccination coverage > 80% show that the benefits of rubella vaccine outweigh the costs, particularly when combined with measles vaccination.⁸

It must be noted that the United State had its own devastating bout of rubella when over 60,000 children were born deaf. The US controlled the disease by widespread use of rubella vaccine. Vaccination against rubella is rare in India, which is an irony since it is the home of the Serum Institute in Pune - the producer of half the world's rubella vaccine requirements. Consultations between infectious disease experts of India and the US suggest that administering the vaccine to pre-adolescent girls could drastically reduce the incidence of rubella and related birth defects.⁹

Vaccination

There is no treatment for Rubella. Vaccination is the only way to prevent all complications of disease. Rubella Vaccine, Live, Attenuated (Freeze-Dried) is prepared using Wistar RA 27/3 strain Rubella vaccine virus. This vaccine virus is propagated on human diploid cells (HDC). The vaccine is lyophilized and is provided with diluent. The product has the appearance of a yellowish white dry cake. The vaccine meets the requirements of WHO when tested by the methods outlined in WHO TRS 840 (1994).¹⁰

Children can be protected against Rubella with a dose of MMR at 12–15 mo. If missed, a child may be vaccinated up to the age of 12–13 y. Moreover, a separate vaccine against Rubella is also available. Rubella vaccine should be given to all girls at puberty (12 y and above), all women of child-bearing age and after delivery. Rubella vaccine is not to be taken by a pregnant woman. Pregnancy must be avoided for 28 d following Rubella vaccine. Rubella vaccine offers long-term protection. Clinical reports state that sufficient antibodies are present in the blood even 21 y after vaccination.⁶

Revaccination

Children first vaccinated when younger than 12 mo of age should be revaccinated. Based on available evidence, there is no reason to routinely revaccinate persons who were vaccinated originally when 12 mo of age or older. However, persons should be revaccinated if there is evidence to suggest that initial immunization was ineffective. Rubella vaccine can be safely and effectively given simultaneously with DTP, DT, TT, Td, BCG, Polio vaccine (OPV and IPV), Hemophilus influenzae type b, Hepatitis B, Yellow fever vaccine and vitamin A supplementation. The vaccine should not be given in acute infectious diseases, leukemia, severe anemia and other severe diseases of the blood system, severe impairment of renal function, decompensated heart diseases, following administration of gammaglobulin or blood transfusions. Since the effect of the live rubella vaccine on the fetus is not known, it is contraindicated in pregnancy.¹⁰

Whereas the developed world has planned to eliminate rubella, India at this juncture with its acclaimed progress in economy and biomedical science should not further delay assessment and analysis of the situation, and should take action to eliminate rubella. Only then can we prevent innumerable stillbirths, abortions and the devastating CRS.¹¹ The Government of India should formulate a policy to vaccinate all children against this disease to prevent CRS. Sero-surveillance of women needs to be continued, and an immunization policy needs to be developed for adolescent girls and/or women of childbearing age before conception in order to control CRS. Vaccination of infants and assuring immunity against rubella in reproductive-age women can achieve the goal of complete prevention of CRS.¹¹