Description of the condition
Rubella, also known as German Measles is an acute viral disease that causes fever and rash (CDC 2011). Rubella was discovered in the 1750s (Cooper 2001) and its teratogenic effect was observed by Gregg in 1941 (Gregg 1991). Further studies confirmed the association with other congenital defects with rubella such as cataracts, deafness and congenital heart defects (Overall 1998).
The rubella virus is an RNA virus (CDC 2005) that is transmitted by droplets and can be transmitted and replicated in the placenta during maternal viraemia, which usually occurs five to seven days after maternal infection. The infection of the fetus can occur at any time during pregnancy but the outcome depends on the gestational age at which the infection takes place (Duszak 2009). There is no risk to the fetus if rubella infection occurred before conception (Enders 1988). However, if rubella infection occurs during pregnancy, the virus spreads through the blood and multiple maternal tissues may be infected including the placenta. Subsquently, maternal antibodies get rid of the virus from the blood but it may persist for months in the placenta. About 80% of fetuses exposed to the rubella virus at or before 12 weeks of pregnancy will become infected and 85% of them will develop congenital rubella infection. Most of the infections occur during the first eight weeks, with rapid decline in the risk of congenital infection after 12 weeks' gestation (Miller 1982).
During the first 12 weeks of pregnancy, when the fetus is incapable of producing immunoglobulin (IG), maximum damage can occur in 80% of fetuses (Webster 1998). In the second trimester, the risk of fetal infection decreases significantly to 25%. This is due to the well developed immune response of the fetus and the structural changes of the placenta leading to increased resistance to the rubella virus. In the last trimester of pregnancy, the rate of fetal infection rises back to 100%, but fetal damage is rare due to the fully developed immune system of the fetus (Webster 1998).
Congenital rubella infection may result in intrauterine fetal death, premature delivery or congenital rubella syndrome (CRS). The classic CRS is characterised by deafness, cataract and congenital heart defects. Other manifestations of the congenital rubella infection may be found in newborns and infants as developmental and late-onset anomalies. Such abnormalities can be permanent structural defects, or transient abnormalities; permanent abnormalities include heart and eye defects, central nervous system abnormalities and deafness. Transient manifestations include poor growth of baby during pregnancy (intrauterine growth restriction), loss of transparency of cornea (cloudy cornea), enlargements of the baby's liver and spleen (hepatosplenomegaly), low platelets level (thrombocytopaenia) and an infection or inflammation of brain (meningoencephalitis) (Plotkin 2011).
In 1969, the rubella virus was isolated and the first successful vaccine was approved in the United States of America (USA), with subsequent reduction in rubella infection and CRS (Duszak 2009). Despite many national, rubella-containing vaccine (RCV) immunisation programmes, the burden of CRS still exists and it is estimated that about 238,000 children are born with CRS each year, with the majority reported in the developing countries (Vijayalakshmi 2002). In contrast, during the years 2001 to 2004, only five infants with CRS were reported in the USA (Reef 2006).The proportion of women of childbearing age who are susceptible to the rubella virus infection varies greatly among nations and depends on the population density. In areas with low-density population and low risk of contacting the rubella infection, more women are susceptible at childbearing age to the rubella virus, whereas women in crowded urban areas develop immunity secondary to infection early during their childhood (Plotkin 2004).
Description of the intervention
The first three vaccines developed for rubella were withdrawn from the market due to the high incidence of side effects including arthritis, neuropathy and arthralgia (joint pain), and were replaced in by the RA27/3 (human diploid fibroblast) vaccine when it was licensed in 1979. RA 27/3 rubella vaccine is a live attenuated virus and was first isolated in 1969 (Preblud 1980) and is currently the only licensed vaccine in USA and most of the world (Preblud 1980). Rubella vaccine is available as a single vaccine or in combination with other vaccines such as measles and mumps (MMR), or mumps, measles, and varicella vaccine (MMRV).
MMR and MMRV are provided as a lyophilised (freeze-dried) powder and reconstituted with 0.5 mL sterile water, preservative free. The vaccine contains a small amount of human albumin (Kroger 2011). RCVs should be stored in the refrigerator at 2 to 8oC and the diluents (sterile water) can be stored with the vaccine in the refrigerator or at the room temperature. The vaccine is given as a subcutaneous injection in the deltoid muscle (Kroger 2011). Because the rubella vaccine is a live attenuated vaccine, it is not given during pregnancy due to the theoretical risk of congenital infection (Zimmerman 2007), and women should be counselled to avoid pregnancy for four weeks after rubella vaccination. However, if pregnancy occurs during this time it is not an indication to terminate the pregnancy (CDC 2007). Pregnant women should be screened, and those who are found to be sero-negative should be offered the MMR vaccine in the postpartum period to prevent congenital rubella infection during the subsequent pregnancies.
Around 2% of RCV recipients develop all or some of the following side effects; post auricular swelling, cough, rhinitis, and influenza like illness, while 4% may develop allergy and fever. A rare side effect is severe allergic reaction (anaphylaxis) (Castro 2005).
Usually after vaccination, sero-conversion is induced in more than 95% of the vaccinated population (Weibel 1980). However, only two-thirds of the vaccinated population continue to have lifelong immunity against rubella infection (Johnson 1996). Hence, a considerable proportion of women who were vaccinated during childhood will be susceptible to rubella infection by the time they reach childbearing age. For instance, sero-negativity among women of childbearing age was 23% in Nigeria in women vaccinated in childhood (Onyenekwe 2000),14% in Taiwan (Lin 2010) and 6.7% in Japan (Okuda 2008); while 15% of unvaccinated population in Turkiy were sero-negative (Aksit 1999), which indicates a variable response to childhood vaccination in different communities.
Postpartum rubella vaccination is recommended to reduce the risk of congenital rubella infection in subsequent pregnancies (Canadian NACI 1998; Watson 1998). This strategy has advantages as women are vaccinated while in hospital, thus increasing the uptake of vaccination. In addition, the fecundity rate is reduced during the postpartum period, giving the mother time to build immunity against rubella (Valeggia 2009). However, studies have documented a poor compliance to postpartum rubella vaccination of sero-negative women; with resultant CRS in subsequent pregnancies (Schluter 1998). Additionally, earlier reports have linked postpartum rubella immunisation to an increased rate of arthritis (Tingle 1985) but recent reports did not find the condition to be more prevalent in vaccinated women than those who were not vaccinated (Ray 1997).
The strategy of postpartum rubella vaccination entails screening of all women who attend for delivery in any health facility to detect those who are sero-negative then to offer them vaccination. However, the cost of screening for sero-negative and immunisation of women of childbearing age, might be a major barrier for implementing such a strategy in many countries with limited resources (Onakewhor 2011).
How the intervention might work
The RA27/3 rubella vaccine is well tolerated, and induces sero-conversion in more than 95% of those vaccinated (Weibel 1980). Hemagglutination inhibition (HAI) antibodies typically develop 10 to 28 days after vaccination (Meegan 1983). The HAI antibodies are specific for three structural proteins, the virus capsid (C protein) and envelope proteins E1 and E2, and can be detected one month after vaccination. However, about 5% of those vaccinated fail to sero-convert (Best 2007).
Why it is important to do this review
In the year 2000, the World Health Organization (WHO) introduced RCV into the national childhood immunisation program, and 130 member countries out of 195 joined the program. Consequently, the incidence of rubella decreased by 82% in developed countries. Nevertheless, around 10% to 20% of the post-teenager populations remain susceptible to rubella in developed countries, and up to 68% are susceptible in developing countries (Karakoc 2003). It is estimated that CRS affects 283,000 infants every year (Vijayalakshmi 2002). This is due to rubella re-infection, lack of universal vaccination, and the primary and secondary vaccine failure (Miller 1991). Hence, screening women during pregnancy to identify susceptible women and vaccinating them is expected to reduce the incidence of CRS further.