Rubella threat hasn’t gone away you know

Rubella – or German measles – was long considered innocuous. A mild childhood infection among children aged four to nine years, it typically caused a transient rash and swollen glands.

But everything changed on October 15th, 1941. That's when Australian ophthalmologist Norman Gregg addressed the Ophthalmological Society of Australia, reporting how an unusually high number of infants with congenital cataracts and other abnormalities were born in Sydney, and elsewhere in Australia. Gregg's crucial observation was that in most cases, the infants' mothers had contracted rubella in the first three months of pregnancy, during a widespread epidemic of the disease.

Gregg’s findings were repeated elsewhere, confirming that if non-immune females of childbearing age contract rubella during early pregnancy, the foetus can be damaged. For example, rubella infection in the first 12 weeks of pregnancy carries a 90 per cent risk of congenital abnormalities, and manifestations of the congenital rubella syndrome (CRS) include cataracts, cerebral palsy, congenital heart disease and deafness. Maternal infection between 13 and 16 weeks carries a 17 per cent risk of congenital abnormalities in those infected; and although infection after 16 weeks is not usually associated with congenital abnormalities, deafness has occurred following infection at 22 weeks.

The rubella virus was first isolated in 1962, and by 1965 vaccine trials had begun in the United States. The aim of rubella vaccination is to protect women of childbearing age, and in Ireland a single rubella vaccine for pre-pubertal girls was introduced in 1971. This was followed in 1988 by the one-dose measles, mumps and rubella (MMR) vaccine, and succeeded by a two-dose vaccine in 1992.

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According to the Health Service Executive, the MMR vaccine should be given at least one month before pregnancy.

Susceptible women

The success of rubella vaccination can be gauged from the fact that, in Ireland, there were 106 recorded cases of CRS between 1975 and 1990; two recorded CRS cases between 1991 and 2000; and in April 2016 the World Health Organisation declared Ireland rubella-free. Nevertheless, antenatal rubella antibody screening continues in Ireland, aiming to identify susceptible women who would benefit from postnatal MMR vaccination, thus conferring protection against rubella infection in future pregnancies.

In a recent study published in the Irish Journal of Medical Science, Dr Ciara O'Connor and colleagues analysed the concentration of rubella antibodies in 25,264 antenatal blood samples taken from women attending Dublin's Rotunda Hospital between January 2015 and June 2017. The study had two aims: first, to determine the percentage of pregnant women who remained susceptible to rubella virus infection; and second, to consider the best use of rubella vaccination resources.

A rubella antibody concentration of zero to 4.9 International Units per millilitre of blood plasma (IU/ml) indicates susceptibility; 10 IU/ml or more indicates immunity; and readings between 5.0 and 9.9 IU/ml are considered ‘equivocal’.

The study showed that 88.7 per cent of women were immune; 2.8 per cent were susceptible; and 7.3 per cent had equivocal results. A significant finding was that there has been a decline in protective rubella antibodies in this population, with O’Connor and colleagues observing: “The majority of antenatal women in this study are rubella immune, but we have identified a rubella susceptible cohort of younger adults now presenting to maternity services. These women are at greater risk of CRS and also pose a potential risk for the re-emergence of rubella in Ireland.”

The authors, perhaps unsurprisingly, found that high vaccine uptake in the mid-1970s and early 1980s was reflected in the fact that 90 per cent of women born between 1979 and 1983 were immune. By contrast, the study found that women born between 1990 and 1999 have lower levels of rubella immunity, and the researchers comment that the number of those susceptible women with rubella antibody concentrations of less than 5 IU/ml “is likely to increase further in the coming years, as [sic]due to poor MMR uptake in the late 1990s following the now-discredited scare regarding the MMR vaccine.”

MMR vaccine and autism

This refers to the fraudulent 1998 Lancet paper by Andrew Wakefield (later struck off the UK Medical Register) and colleagues, claiming a link between the MMR vaccine and autism. The Oireachtas Joint Committee on Health and Children in its Report on Childhood Immunisation (2001) concluded there was no evidence for a proven link between MMR vaccine and autism.

Dr O'Connor and colleagues consider it appropriate to end rubella antenatal screening in Ireland (as is the case in Scotland, Wales and England): "As 50 per cent of pregnancies in Ireland are unplanned, resources could be re-directed to general practitioners, practice nurses and family planning clinics to enable the education of women of childbearing age contemplating pregnancy to get their MMR status checked and also to offer opportunistic rubella antibody testing to all women of childbearing age."

They further encourage free provision of phlebotomy – taking blood – and MMR vaccination as incentives to increase vaccine uptake. Highlighting a 2013 Irish study which found that younger women, first-time mums and non-EU nationals were most at risk, the researchers note: "Special attention should be paid to encouraging women living in Ireland but born outside Europe to get vaccinated as they are more likely to be rubella seronegative."

Since Norman Gregg’s discovery of the hazards of rubella virus infection in pregnancy, rubella vaccination has changed the epidemiology of the disease, and vaccination strategies continue to evolve.

Given this shifting virological landscape, it is clear that continuing research into rubella during pregnancy will help shape public-health policy.