In 1941, an epidemic of congenital cataracts in Australia was observed in the wake of a large outbreak of rubella.1 Until then, Rubella was considered a mild and self-limited illness. However, it assumed new importance when the association with congenital cataracts demonstrated its ability to induce congenital malformations in infants born to susceptible women who acquired rubella during pregnancy. In the following years, a broad spectrum of congenital malformations associated with congenital infection and Congenital Rubella Syndrome (CRS) were described.2-4 The subsequent success in developing and licensing an effective vaccine to prevent rubella in 1969 remains a major public health achievement. Until recently, however, the use of rubella-containing vaccine has occurred mainly in developed countries. According to the World Health Organization (WHO) only 99 (51%) countries/territories were using rubella vaccine in their national immunization programs in 2000,5 but by February 2019, 168 (87%) countries reported using rubella-containing vaccine in their national programs.6
ETIOLOGICAL AGENT, IMMUNOLOGY, AND DIAGNOSIS
Rubella disease (also known as German measles or 3-day measles) is caused by an RNA virus of the Togavirus family. This family also includes Eastern and Western Equine Encephalitis viruses. Rubella virus is highly communicable, though less so than measles or varicella viruses, and humans are the only known reservoir. It is transmitted by the respiratory route, and infection usually occurs as a result of droplet spread through nasopharyngeal secretions of infected persons.
Primary rubella infection induces lifelong immunity. Rarely, reinfections with rubella virus have occurred in persons with natural or vaccine-induced immunity, but they are usually asymptomatic and recognized only by serological testing.7 Reinfections in pregnant women pose minimal risk to the unborn fetus.7-9
Clinical diagnosis of rubella disease is unreliable without laboratory confirmation because rubella infection is frequently asymptomatic or presents as a mild illness with a nonspecific rash. A history of exposure to rubella can be helpful in the absence of the full complement of clinical signs and symptoms. Serologic testing is the simplest means of confirming rubella infection. Both antirubella immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies appear shortly after the onset of rash. IgM antibodies generally do not persist more than 8–12 weeks after rash onset, while IgG antibodies usually persist for the lifetime of the patient. Rubella virus is present in a variety of clinical specimens from infected persons. However, some intrinsic characteristics make detection of rubella virus more challenging than detection of measles virus, which causes a similar febrile rash illness. Rubella infection usually results in a lower-titer viremia, making it more challenging to grow virus in cell culture. Rubella virus has a higher G-C content in its RNA than measles, thus making it more difficult to detect by reverse transcriptase-polymerase chain reaction (RT-PCR).10
Approximately 84% of neonates with congenital rubella infection have detectable rubella virus, and virus can be found in ...