4.3 Interpretation of IgM results among suspected cases with recent vaccine history

Mick Mulders

The true case status of suspected cases of measles or rubella among individuals who were vaccinated between 8-56 days prior to rash onset cannot be determined by testing for the presence of IgM. The virus-specific IgM detected by EIA does not distinguish between IgM elicited by a current wild-type infection by measles or rubella and the IgM response due to recent immunization. While virus-specific IgM antibodies produced following vaccination in most individuals will decline to undetectable levels at 28-56 days post immunization (or following natural disease), the use of assays with higher sensitivity may extend the period that IgM can be detected. Low levels of rubella IgM have been detected for months or years following infection or vaccination in some individuals [6].

A special situation applies to suspected measles or rubella cases that present with rash from 7-14 days after receipt of the measles monovalent or combination MR/MMR vaccine. While this timeframe is typical for a measles vaccine reaction, there may be contemporaneous measles activity or risk factors for exposure that raise the index of suspicion of a wild-type infection. While most rashes from vaccination are due to the measles component of MR or MMR vaccines, a vaccine-associated rash due to the rubella component of MR/MMR vaccine strain is possible, which extends the range that rash can develop following vaccination from 14 days to 30 days after receipt of rubella-containing vaccine.

The IgM response to the measles component of the vaccine typically precedes the IgM response to the rubella component by up to a week or more [3]. Therefore, in the first or second week after vaccination, a positive IgM result may be obtained for measles while rubella IgM is negative. These results should not be interpreted as evidence of a measles wild-type infection. Because serologic techniques cannot distinguish between an immune response to natural infection and antibodies elicited by a recent immunization, collection of clinical specimens for molecular testing are critical to determine the genotype.

If epidemiologic and clinical criteria for a vaccine-related rash are met, it is possible that a suspected case with a recent measles vaccination may be attributed to a vaccine reaction and discarded without identification of a vaccine strain by molecular testing. Since serology cannot discern a wild type infection from vaccination, the case must be investigated appropriately. However, further evaluation of the case may provide evidence for a vaccine-related rash. It is noted that a rash that occurs 7-14 days post-vaccination may be due to an infection with another rash-causing illness rather than a reaction to the recent vaccination. However, if the case meets the criteria for a vaccine-related rash, the rash is generally attributed to the vaccine unless laboratory confirmation of another cause of rash is identified.

Suspected cases that could potentially be discarded as having a rash due to vaccine would generally be limited to sporadic cases and would not include those individuals who received vaccination as post-exposure prophylaxis (PEP), or were immunized as part of an outbreak response. In such instances, when genotyping is not available to confirm a vaccine strain, the case would be confirmed as measles by the positive IgM result. The rationale for confirmation of the case is that the patient was either epidemiologically linked to a confirmed case or was temporally associated with an outbreak. Although PEP is recommended as a control measure, the protective efficacy of post-exposure immunization has not been well documented. The guidelines for case classification of a suspected case with a positive IgM result and a recent MR/MMR vaccination are given in the box below.

Criteria for vaccine-associated rash

The following 5 criteria must all be met for a rash from a suspected case with a positive or equivocal IgM result to be attributed to a reaction from a recent vaccination. These criteria are provided for those situations where genotyping was unsuccessful or an appropriate virologic specimen was not collected.

  1. The patient had a rash illness, with or without fever, but did not have cough or other respiratory symptoms
  2. The rash developed 7-14 days after vaccination with a monovalent measles or MR/MMR vaccine
  3.  The blood specimen, which was positive for measles or rubella IgM, was collected 8-56 days after vaccination
  4.  A thorough field investigation did not identify any secondary cases of measles/rubella
  5. Field and laboratory investigations failed to identify other causes for the rash illness

If all criteria are met, the case should be recorded as a vaccination-related rash case and discarded.