Dilemmas and Pitfalls in Rubella Laboratory Diagnostics in Low Prevalence or Elimination Settings

Charlton, Carmen; Severini, Alberto

doi:10.1007/s40506-016-0090-8

Cited by 7 publications

(5 citation statements)

References 68 publications

(63 reference statements)

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“…RT-PCR can be used to detect measles in urine specimens up to several weeks after disease onset, providing a non-invasive specimen option, which can also be used for genotyping [ 33 ]. Avidity testing can provide important contextual information, since samples from recently infected individuals would have low IgG antibody avidity, while those from those infected or immunized in the past would have high IgG antibody avidity [ 16 ]. For measles, plaque reduction neutralization tests of high avidity sera can be used diagnostically, with high concentrations of neutralizing antibodies being indicative of true cases [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Polymerase chain reaction (PCR) can be used for direct detection of virus, but may not be available in all settings [ 13 ]. Avidity testing and plaque reduction neutralization testing of high-avidity samples may provide important additional information and also be a means of diagnosis in low-burden settings [ 15 , 16 ]. Serological Immunoglobulin M (IgM) testing using either capture or indirect enzyme immunoassays [ 14 ] has been a standard laboratory method for diagnosis of acute measles and rubella infections, since it is more readily available than PCR, and faster and less technically challenging than viral culture [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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The utility of measles and rubella IgM serology in an elimination setting, Ontario, Canada, 2009–2014

et al. 2017

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In Canada, measles was eliminated in 1998 and rubella in 2000. Effective measles and rubella surveillance is vital in elimination settings, hinging on reliable laboratory methods. However, low-prevalence settings affect the predictive value of laboratory tests. We conducted an analysis to determine the performance of measles and rubella IgM testing in a jurisdiction where both infections are eliminated.21,299 test results were extracted from the Public Health Ontario Laboratories database and 1,239 reports were extracted from the Ontario Integrated Public Health Information System (iPHIS) from 2008 and 2010 for measles and rubella, respectively, to 2014. Deterministic linkage resulted in 658 linked measles records (2009–2014) and 189 linked rubella records (2010–2014). Sixty-six iPHIS measles entries were classified as confirmed cases, of which 53 linked to laboratory data. Five iPHIS rubella entries were classified as confirmed, all linked to IgM results. The positive predictive value was 17.4% for measles and 3.6% for rubella. Sensitivity was 79.2% for measles and 100.0% for rubella. Specificity was 65.7% for measles and 25.8% for rubella.Our study confirms that a positive IgM alone does not confirm a measles case in elimination settings. This has important implications for countries that are working towards measles and rubella elimination.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The utility of measles and rubella IgM serology in an elimination setting, Ontario, Canada, 2009–2014

et al. 2017

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“…(P-value = 0.14). (which is low) is diagnosed as prenatal infection (8). The virus can be recovered from the posterior pharynx and conjunctiva, CSF, or urine.…”

Section: Resultsmentioning

confidence: 99%

Lessons from ten years searching the Congenital Rubella Syndrome (CRS) cases in young population of a developing country: Tehran; Iran.

Vafaee-Shahi

Noorbakhsh

Tahernia

et al. 2021

Preprint

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Background: Maternal infection with rubella in the first trimester of pregnancy can result in developmental abnormalities in fetus such as hearing loss, heart abnormalities, impaired vision, and mental retardation. Methods: This Multi-stage prospective/cross sectional study was carried out in three stages in three educational hospitals in Tehran (Rasoul akram, Akbar Abadi and Firoozabadi), during 2011-2012: In first stage, 186 infants at birth day. Rubella antibodies (IgG&IgM) in cord blood was evaluated by Eliza method. In second stage, 89 infants suspected INTRA UTERINE INFECTION and in third stage 165 infants with SNHL were selected . Age matched control group were selected and examined concurrently. Rubella antibodies (IgG&IgM) compared between cases and healthy matched infants. Results: In first stage, significant correlation was found between vaccination history and rubella immunization of mothers (P value = 0.001). None of those with a history of vaccination had positive IgM. In second stage, confirmed CRS (positive IgM) was found in 4.4% of total CRS suspected cases (5 /89). The positive RT–PCR detected in 1.5% of total CRS suspected cases (1/89). Except a positive correlation between abnormal neurologic findings and positive IgM in Confirmed CRS cases, other clinical findings were not related to serologic tests. In third stage, the highest frequency for Positive Rubella-IgM observed in the SNHL cases <1 year old (P-value = 0.14). Rubella-IgG was significantly higher in age group < 1 years (P-value = 0.001). There was no significant difference for Rubella-IgM (P-value = 0.6) between SNHL cases and controls but a significant (P-value = 0.000) difference was observed for Rubella-IgG which was more frequent in control group.Conclusion: Active CRS surveillance is recommended strongly even in country with full rubella vaccination. Without active CRS surveillance ;CRS especially, mild infection ( not classic form) such as IUGR(intrauterine growth retardation), hearing loss, heart abnormalities, impaired vision, and mental retardation even in developed country might be missed . The necessity to add a booster vaccine dose to the national vaccination program 8 years after the last vaccination should be evaluated if needed. In addition, follow-up of safety status and studies to evaluate the success of the program may be necessary and is recommended.

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“…In summary, none of the methods for detecting anti-rubella IgM antibody evaluated in this study had the combination of high sensitivity and high specificity that is needed to support monitoring of elimination goals, although this could be somewhat compensated for by taking a presumptively positive approach to specimens with equivocal results (particularly Microimmune and Euroimmun glycoprotein methods). These underperforming methods, when combined with low rubella prevalence in elimination settings, lead to poor predictive ability and are therefore of limited value ( 5 , 6 , 21 – 23 ). A study conducted in the province of Ontario, Canada, a setting without endemic circulation of rubella, reported that the positive predictive value of a positive rubella IgM test for case confirmation was 3.6% ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…Historically, this was often achieved through detection of rubella specific IgM antibodies although it has been augmented or replaced by virus detection by RT-PCR, particularly in countries approaching or having achieved elimination (3)(4)(5)(6). Nonetheless, IgM serology remains an important tool in many countries where it can be used for case confirmation (endemic settings) and active disease surveillance (case finding in elimination settings) through reflex or co-testing of sera captured through other surveillance systems, such as measles and arboviruses (7,8).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Rubella Virus-Specific IgM Antibodies

et al. 2022

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Rubella and congenital rubella syndrome are caused by the rubella virus and are preventable through vaccination, making disease eradication possible. Monitoring of progress towards global eradication and local elimination requires high quality, sensitive disease surveillance that includes laboratory confirmation of cases. Previous evaluations of anti-rubella IgM detection methods resulted in the broad adoption of Enzygnost (most recently manufactured by Siemens) enzyme-linked immunosorbent assay (ELISA or EIA) kits within WHO’s global measles and rubella laboratory network but they have been discontinued. This study evaluates seven comparable ELISA methods from six manufacturers (Trinity Biotech, Euroimmun, Clin-Tech, NovaTec and Virion\Serion) as well as one automated chemiluminescent assay (CLIA) from Diasorin. These methods consisted of three IgM capture methods and five indirect ELISA methods. A panel of 238 sera was used for the evaluation that included 38 archival rubella IgM positive sera and 200 sera collected from symptomatically similar cases, such as measles, dengue, parvovirus B19 and roseola. With this panel of sera, the sensitivity of the methods ranged from 63.2% to 100% and the specificity from 80.0% to 99.5%. No single method had both sensitivity and specificity >90%, unless sera with equivocal results were considered to be presumptive positive. Some methods, particularly the Serion ELISA, had a large number of false positives with parvovirus B19 IgM positive sera as well as sera from confirmed measles cases. The performance characteristics identified in this evaluation serve as a reminder to not rely solely on rubella IgM results for case confirmation in elimination settings.

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Dilemmas and Pitfalls in Rubella Laboratory Diagnostics in Low Prevalence or Elimination Settings

Cited by 7 publications

References 68 publications

The utility of measles and rubella IgM serology in an elimination setting, Ontario, Canada, 2009–2014

The utility of measles and rubella IgM serology in an elimination setting, Ontario, Canada, 2009–2014

Lessons from ten years searching the Congenital Rubella Syndrome (CRS) cases in young population of a developing country: Tehran; Iran.

Evaluation of Diagnostic Accuracy of Eight Commercial Assays for the Detection of Rubella Virus-Specific IgM Antibodies

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