Persistent fetal rubella vaccine virus infection following inadvertent vaccination during early pregnancy

Abstract

Inadvertent immunisation of seronegative women with RA27/3 rubella virus live-attenuated vaccine several weeks before and after conception is described. Whereas in 5 cases the vaccine virus was not transmitted vertically, in 1 case vaccination led to the development of persistent fetal infection with prolonged virus shedding for more than 8 months. Sequence analysis carried out on isolates from amniotic fluid, from cord blood leukocytes as well as from infantile urine confirmed an infection by the vaccine strain. At birth, the newborn infant exhibited none of the symptoms compatible with the congenital rubella syndrome and signs indicative for development of late onset disease are not apparent. This observation constitutes the first unequivocal documented case of rubella vaccine virus related to persistent fetal infection.

Vaccines and immunoglobulins

“…A persistent subclinical infection was diagnosed in one case (Hofmann 2000). In none of the children with rubella IgM antibodies was CRS detected.…”

Congenital rubella syndrome after rubella vaccination in 1–4 weeks periconceptional period

“…19 There are other similar reports that have shown in a few of susceptible mothers inspite of lack of signs of CRS at birth and longer follow up laboratory signs of rubella infection were evident. 20,21,22 While no case of clinical CRS has ever been reported following rubella vaccination in early pregnancy , in some reports subclinical reinfection with natural rubella virus in pregnant mothers with previously acquired immunity to the disease has caused CRS. 23,24 Of course reinfection is more common amongst people previously immunized via vaccination, not viral infection and who have a serum antibody titer of 1/64 or less.…”

Safety of Administering Live Vaccines during Pregnancy: A Systematic Review and Meta-Analysis of Pregnancy Outcomes

“…Additionally, twenty-three uncontrolled cohorts [8,[10][11][12][13]22,32, describing pregnancy outcomes after maternal vaccination were retrieved in the literature search. No cases of fetal vaccinia were found among 643 women vaccinated against smallpox [8,58,59], and rates of adverse pregnancy outcomes were within expected limits, except for a high frequency of stillbirth among those vaccinated in the first trimester [59] (Table S7).…”

“…Two controlled and twelve uncontrolled studies reported on the prevalence of CRS after maternal immunization [10][11][12][13]22,32,[38][39][40][41][42][43]60,61], as shown in Table S8. No cases were detected among 3918 infants, including 2303 born to women susceptible to rubella before vaccination.…”

“…With regards to rubella vaccine, there is evidence of vertical transmission and subclinical fetal infection, as demonstrated by immunoglobulin M (IgM) titers in cord blood of exposed infants [10][11][12], and more recently by molecular methods [13].…”