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

Abstract

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.

Public health responses during measles outbreaks in elimination settings: Strategies and challenges

“…2 , 92 In the absence of clinically compatible symptoms or a clear epidemiological link to a laboratory-confirmed case, false-positive IgM results are common. 2 , 92 Thus, it is important to restrict laboratory testing to persons likely to have measles (e.g., those with a febrile rash illness and risk factors such as travel or being unvaccinated) and to obtain routinely specimens for RT-PCR testing along with serological samples. 1-3 In this context, when confirming a diagnosis of measles with a positive IgM, Canada has specified the requirement of an appropriate exposure (epidemiological-link to another case or travel history), in addition to measles-compatible symptoms.…”

“…1-3 In this context, when confirming a diagnosis of measles with a positive IgM, Canada has specified the requirement of an appropriate exposure (epidemiological-link to another case or travel history), in addition to measles-compatible symptoms. 2 , 92 Conversely, because measles is rare in elimination settings, suspected cases with a positive IgM necessitate detailed epidemiological investigations for an unrecognized exposure, and they may require additional diagnostic testing before being ruled out. 2 , 4 , 92 …”

“…2 , 92 Conversely, because measles is rare in elimination settings, suspected cases with a positive IgM necessitate detailed epidemiological investigations for an unrecognized exposure, and they may require additional diagnostic testing before being ruled out. 2 , 4 , 92 …”

Immune surveillance for vaccine-preventable diseases

“…Upon initial activation B cells produce IgM and during further differentiation could undergo class switch recombination resulting in the production of IgG or IgA ( Figure 1). Therefore, detecting specific IgM can be an indication of recent exposure to a pathogen or antigen of a pathogen [51,52]. For most vaccines, especially vaccines administered intramuscularly, the majority of B cells will switch toward the production of IgG [53].…”

“…Mucosal vaccination or infection will also induce IgA (not depicted). Changes in pathogens related to antigenic drift/shift, or immunity/vaccine escape and rubella indicated that this approach is insufficient to assess new infections [51]. Moreover, the kinetics of IgM induction following exposure to a new pathogen may also change with age, as observed in a novel influenza infection in the USA, where young individuals induced IgM whereas older individuals showed no significant changes in IgM production, probably due to cross-reactive antibodies to previously encountered influenza viruses [75].…”