Rubella virus infection is typically diagnosed by the identification of rubella virus-specific immunoglobulinSymptomatic rubella is characterized by a mild fever and a maculopapular rash of short duration. The clinical diagnosis of rubella is unreliable, and many rash illnesses, such as those caused by measles virus and parvovirus B19, mimic rubella (2). Therefore, laboratory confirmation is essential for the diagnosis of rubella and is typically done by testing serum samples for rubella virus (RV)-specific immunoglobulin M (IgM) antibodies. Serum IgM and IgG responses to RV develop rapidly in the first few days after the onset of rash. However, approximately 50% of samples collected on the day of rash onset test negative for RV-specific IgM antibodies (1, 9, 17). Often, only a single serum sample taken near the time of rash onset is available, resulting in the lack of serologic confirmation of many rubella cases. Thus, the development of a rapid laboratory diagnostic tool for the confirmation of rubella within the first few days of symptom onset would improve the ability to confirm rubella.The isolation of virus in cell culture or the detection of viral RNA by reverse transcription-PCR (RT-PCR) also provides reliable evidence of RV infection (26). Unfortunately, blood is not a good sample for use for the detection of RV, because the highest viral titers in blood typically occur before the onset of rash and virus is undetectable in blood by 2 days after rash onset (6). The virus titer in throat swabs, however, usually reaches a peak titer on the day of rash onset and the titers in throat swabs decline more slowly than those in blood, so that virus can be detected for up to 5 to 7 days after rash onset (6). Several RT-PCR assays for the detection of the RV genome in clinical samples have been described (3,7,15,16,20,25). Templates for the determination of viral sequences for molecular epidemiology can also be made by using RT-PCR.The use of alternative specimens could help reduce the obstacles to specimen collection, storage, and transport in the field (22). Oral fluid (OF), which is collected by rubbing an absorptive device between the gum and the cheek, can be obtained by a method that is relatively noninvasive, is easier to obtain than blood, and has the advantage that it can be used for both RVspecific antibody detection and RV genome detection (12,19,20). Currently, in the United Kingdom, OF samples from notified clinically diagnosed cases are collected between 1 and 6 weeks after the onset of symptoms and are transported by mail to the Central Public Health Laboratory, where they are tested for specific antibody and viral RNA by RT-PCR. By the use of this strategy, specimens from 54.6% of rubella notifications from 1995 through 2001 were obtained for laboratory testing and specimens from 12.7% of the rubella notifications were confirmed to represent rubella cases (20,21).
Most persons with rubella virus-specific immunoglobulin M (IgM)-or IgG-positive sera tested positive (98% [n ؍ 178] and 99% [n ؍ 221], respectively) using paired filter paper dried blood spot (DBS) samples, provided that DBS indeterminate results were called positive. For persons with IgM-or IgG-negative sera, 97% and 98%, respectively, were negative using DBS.Simplification of specimen collection, storage, transport, and processing in the field would be a great advantage to rubella surveillance. Recent studies have suggested that filter paper dried blood spots (DBS) are suitable for laboratory detection of measles-specific immunoglobulin M (IgM) (2,3,(6)(7)(8). In this study, we compared the detection of rubella virus-specific IgM and IgG in DBS to their detection in serum samples collected from health care provider-diagnosed rubella patients.The presence of rubella virus-specific IgM in serum according to enzyme immunoassay is diagnostic for rubella, and thus, results from sera were used as the standard. However, because most specimens were collected in the first week after rash onset, a time period when serum IgM and IgG enzyme immunoassays do not detect many rubella cases, we do not refer to serum samples as a "gold standard" (1, 9). Health care workers at the local health care centers in five Regional Health Directorates in Peru enrolled persons 8 months or more in age seen within 28 days of rash and fever onset (clinically suspected rubella). Persons who were vacci-* Corresponding author. Mailing address: Centers for Disease Control and Prevention,
The proportion of postpartum women at the study sites who were found to be susceptible to rubella was 12.8%, placing Peru among the countries facing a moderate level of risk for the occurrence of CRS cases. The findings suggest the need to also provide the rubella vaccine to other population groups, especially women of childbearing age.
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