Congenital Viral Infections Slide Set
Prevention of Rubella Infections
The first vaccines were developed in the early 60's (HPV77.DE5 and Cendehill) and were licensed for use in 1969. In 1979 the HPV77.DE5 strain was replaced with RA27/3 and Cendehill is no longer available. RA 27/3 is now the most widely used vaccine strain and is made by 7 manufacturers. All vaccines are administered subcutaneously and are well tolerated and produced a response in 95% of recipients. Although the virus is excreted by vaccines, it is not transmitted to susceptible contacts.
1. Vaccination Policies
Two main policies were initially used:-
Universal childhood vaccination was adopted by the USA in 1969 with great success. It was offered as part of the MMR (Mumps, Measles, Rubella) vaccine. The uptake was very high as proof of immunization of measles is mandatory before school entry. Since 1978 there has been a steady decline in CRS as well as postnatally acquired rubella and CRS is on verge of being eliminated in the USA. The USA policy results in financial saving: cost-benefit analysis shows that the cost of rubella in an unvaccinated population is approx. 11 times more than the cost of vaccination policy.
In the UK selective vaccination of 11 - 14 yr old girls was introduced in 1970. The vaccine was also offered to susceptible people eg.nurses, doctors and schoolteachers and to women who were found to be seronegative when they attended antenatal clinics. Seronegative women attending antenatal clinics were offered vaccination in the immediate postpartum period. It appears that overall 90% of schoolgirls have been vaccinated. However there are districts where the uptake rates are lower. The proportion of susceptible women attending antenatal clinics between 1984 to 1986 varied between 2.3% and 5.8%. Although there has been some decline in cases of reported CRS, maternal rubella is still relatively common. In 1986, 173 cases of laboratory confirmed rubella were reported during the first 16 weeks of pregnancy. A high proportion of these pregnancies were terminated.
Since it became apparent that complete vaccination of the target population was an unrealistic goal and because despite high uptake rates.rubella still infects pregnant women, the rubella vaccination programme in the UK was augmented in 1988 by offering rubella vaccination to preschool children of both sexes. Rubella vaccine is given as part of the MMR vaccine. As part of the " catch up" programme MMR is also given to children age 4 - 5 yrs. The vaccination of 10 to 14 yr olds and seronegative women is to continue until it can be demonstrated that rubella is no longer circulating in the community and that serological surveillance shows that 90-95% of adolescents are already immune. The augmented programme is designed to eradicate rubella. However in the USA this has been harder to achieve than expected. Mathematical models show that poor uptake amongst preschool children may actually increase the proportion of rubella susceptibles in older age groups. Therefore high vaccine uptake is totally essential.
2. Immune responses
Rubella vaccination induces an immune response in 95% of recipients, but antibody concentrations are generally lower after vaccination than after naturally acquired infection. Testing for antibodies should wait until 8 weeks after immunization. Of the 5% who fail to seroconvert, the majority will respond if revaccinated. A few may fail to respond or respond poorly due to concurrent infection or a low level of preexisting antibodies, which may be undetectable by HAI or SRH. Antibodies persists at levels >15 IU/ml in the majority of vaccinees for at least 21 years. In approx. 10% , the Ab levels fall below 15 IU/ml within 5 to 8 years and a small number may become completely seronegative. Rubella specific IgG, IgM and IgG can be detected in the patient's serum. IgM may persists in 73% of vaccinees after 6 mths and occasionally been shown to persist up to 4 years.
Virus excretion can be detected in the majority of vaccinees between 6 to 28 days after vaccination. However transmission of the virus to susceptible contacts rarely occur. It is therefore safe to vaccinate persons who may come into pregnant women. Vaccine virus may also be shed in the breast milk of women who were vaccinated postpartum. However even though some infants are infected, they develop no clinical features. Rubella vaccines are well tolerated. Lymphadenopathy, rash and arthropathy may occur between 10 days and 4 weeks after vaccination. These reactions are less severe than the natural infection. Postpurbertal females are more likely to develop symptoms than children. Like other live vaccines, rubella vaccine should not be given to immunocompromised patients, as a result of disease or treatment.
Pregnancy is an absolute contraindication and pregnancy should be avoided for 1 month after vaccination. Where inadvertent rubella vaccination had occurred just before or during pregnancy, there had no been a single case of fetal damage reported. Even though it has been shown vaccine virus does cross the placenta and establishes a persistent fetal infection. In a series of 486 babies delivered by women who were inadvertently vaccinated during the first trimester, no congenital abnormalities consistent with CRS were reported. However, there was serological evidence of infection in 8 babies
Reinfection with rubella may occur. It is more likely to occur in those whose immunity is induced by vaccination rather than natural infection. The IgG response is highly elevated. A slight and transient IgM response may be present. It has been suggested that IgG avidity assays may be useful in distinguishing between primary and reinfection.
4. Passive Immunization
Post-exposure prophylaxis with immunoglobulins does not prevent infection in non-immune contacts and is therefore not recommended for protection of women exposed to rubella. However it may reduce the likelihood of clinical symptoms which may reduce the level of maternal viraemia and the risk to the fetus. Women who contract rubella during the first trimester of pregnancy but are determined to proceed with the pregnancy may be offered HNIG or rubella immunoglobulin. There is evidence to suggest that infants of women who experienced subclinical rubella in early pregnancy following administration of HNIG is less likely to be infected in utero, or if infected, less likely to be less severely affected. Possible mode of action seems to be decreased maternal viraemia in the presence of HNIG. Dudgeon advocates the administration of HNIG to women who are determined to proceed to term. He suggests a dose of 1500 mg i.m. as soon as possible after exposure and 3 to 4 days later.
Congenital Viral Infections Slide Set