Bollettino epidemiologico nazionale

The 2002 rubella epidemic: one year later

Maria Grazia Revello

Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia.

In 2002 an rubella incidence increased in Italy, and 97 cases of acute infection were diagnosed at the Virology Laboratory of the San Matteo Hospital in Pavia. Thirteen of the 97 cases occurred in pregnant women: 11 were primary infections, and 2 were re-infections in vaccinated women. Infection occurred between one week before the last menstrual period and 28 weeks gestation. Three of the 13 pregnant women were immigrants.

Diagnosis of primary infection was made based on seroconversion or by detection of IgM antibodies plus low avidity IgG (1). Reinfections were diagnosed when a rise in high avidity IgG titer and a transient IgM response were demonstrated.

All 13 pregnancies, 2 of which involved twin gestations, were prospectively followed; women were offered counseling, prenatal diagnosis  and follow up care. Five women (Figure 1 (ita)) underwent prenatal diagnosis at 18-22 weeks gestation by: i) detection of viral RNA in fetal blood and/or amniotic fluid; ii) detection of virus by RT-PCR in tissue cultures; iii) detection of rubella specific IgM antibody in fetal blood (3,4). The same investigations were used to diagnose congenital rubella at birth (detection of viral RNA and/or rubella virus in neonatal blood and urine and of specific IgM antibody in neonatal blood).

Follow-up after one year shows that pregnancy outcomes were poor (Figure 1). While the two previously vaccinated women delivered healthy, non infected newborns, 8 of the 11 women with primary infection either elected to terminate their pregnancies, or had an infected fetus/newborn. In total, 5 cases of rubella transmission occurred, 3 of which were severely affected: these include two fetuses that died in utero at 20 and 29 weeks gestation respectively and 1 liveborn infant affected by unilateral blindness and multiple cerebral lesions. One pregnancy was terminated at 21 weeks gestation following prenatal diagnosis of fetal infection and the detection of cardiac malformations by ultrasound. Finally, the last of the 5 cases involved a liveborn infant with rubella infection confirmed after birth but who is presently asymptomatic at age one. Three women with primary infection at 3-7 weeks gestation elected to terminate their pregnancies before 12 weeks, without performing prenatal screening. Only 4 women with primary infection delivered non-infected newborns; all had acquired rubella in a period at low risk of transmission (from one week before to 11 days after the last menstrual period in 3 cases, and at 28 weeks gestation in one case). Two of these women underwent prenatal diagnosis, which was negative. Had prenatal screening not been available to them, both pregnancies may likely have been terminated.

The medical histories of the 11 primary infection cases (7 nulliparous e 4 multiparous women) reveal that inadequate measures had been undertaken to prevent congenital rubella. Only one of the 7 nulliparous women had been screened for rubella immunity before pregnancy and, although she was found to be seronegative, she had not subsequently been vaccinated. Furthermore, all 4 multiparous women had been found to be susceptible in previous pregnancies and had not been vaccinated in the postpartum period.

An additional case of congenital rubella was identified in an infant who died at 4 months of age and from whom rubella virus from various organs at autopsy. The infant was severely ill at birth, with growth delay, petecchiae, hepatosplenomegaly, cataracts, bilateral deafness, and patent ductus arteriosus, but congenital rubella had not been considered at the time because the mother had been positive for rubella-specific IgG antibodies at 16 weeks gestation.

A scenario similar to the one described above had occurred during a previous rubella outbreak in 1997: 12 rubella cases diagnosed in pregnancy, 6 therapeutic abortions, 2 newborns with congenital infection, one of which symptomatic, 3 healthy newborns and 1 pregnancy with unknown outcome.

Since elimination of congenital rubella is not expected to occur in the short term, it is essential that active surveillance of rubella cases in pregnancy be performed and that qualified laboratory diagnoses be guaranteed. At present, however, few laboratories in Italy are qualified to provide a reliable diagnosis of acute rubella infection (a difficult aspect of which is the interpretation of positive IgM results), and even fewer are equipped with complete up-to-date diagnostic techniques essential for prenatal diagnosis.

It is fundamental that the Italian Health System offer women the possibility to make an informed choice based on appropriate laboratory testing that confirms transmission (or lack of transmission) of infection to the fetus. The availability of qualified laboratory facilities is thus essential if we are to provide women with reliable results and to avoid adding the further trauma of false-negative and false-positive results to an already difficult situation.

References

Hedman K, Rousseau SA. Measurement of avidity of specific IgG for verification of a recent primary rubella. J. Med. Virol. 27:288-292, 1989.

Revello MG, Baldanti F, Sarasini A, Zavattoni M, Torsellini M, Gerna G. Prenatal diagnosis of rubella virus infection by direct detection and semiquantitation of viral RNA in clinical samples by reverse transcription-PCR. J. Clin. Microbiol. 35: 708-713, 1997.

Revello MG, Sarasini A, Baldanti F, Percivalle E, Zella D, Gerna G. Use of reverse-transcription polymerase chain reaction for detection of rubella virus RNA in cell cultures inoculated with clinical samples. Microbiologica 20: 197-206, 1997.