Many suspected cases of measles or rubella that are tested in an elimination setting may not be highly suspicious for these diseases, and yet may be confirmed following detection of virus-specific IgM. For these doubtful cases, without a positive RT-PCR result to corroborate the IgM, there will be increased pressure on the laboratory to conduct additional testing that will provide the evidence needed to discard the case. A checklist is provided below that may be helpful to evaluate the likelihood that the positive or equivocal IgM result was nonspecific or to support a request for additional testing:
- Confirm that the IgM assay used for testing was a validated EIA. If not, the specimen should be referred to a WHO-accredited laboratory and re-tested with a validated EIA
- Confirm that the patient had not received an MR/MMR within 56 days since antibody from immunization could be detectable
- Re-test the serum using a different commercial IgM EIA kit (where available). If the IgM is negative, the case can be discarded
- If serum was collected within 3-4 days of rash onset, test for the presence of measles IgG antibody (or rubella IgG, if suspect rubella case). Detection of IgG is not consistent with a primary infection and could indicate a higher likelihood that the positive IgM result is nonspecific
- If IgM is positive for measles, test for IgM for rubella. If both are IgM positive or equivocal, this may suggest that the IgM result was due to a nonspecific reaction. (The likelihood of simultaneous infection with both viruses is very low)
Details regarding the case may come to light during the course of the investigation and laboratory testing that indicate an alternative etiology. The clinical presentation, patient medical history, and the findings of the epidemiologic investigation may indicate that the positive or equivocal IgM result was obtained due to a non-specific reaction:
- A source of infection for the measles/rubella case could not be identified after a thorough investigation
- Clinical, medical and epidemiologic aspects of the case suggest the rash was due to an alternative etiologic agent, medical condition, or drug reaction (e.g., treatment with antibiotics)
- Identification of a local outbreak of other febrile rash illnesses
In elimination settings, there may be an increase in the proportion of suspected cases that occur as single, sporadic cases in elimination settings. The total number of cases with an unknown source is an important component that is reviewed for the verification of elimination. Frequently, there is a missed opportunity to collect virologic specimens when a sporadic case occurs. This will increase the number of sporadic cases that are confirmed solely due to a positive or equivocal IgM result. If the source of infection is unknown and there is a low index of suspicion, additional laboratory testing may be pursued in an attempt to discard the case as a non-measles, non-rubella case.
For the verification of elimination or as a requirement for countries that have achieved elimination, no more that 20% of confirmed cases* should be categorised as having an unknown source [12,13]. The total number of cases with an unknown source of infection may include some cases for which the genotype was identified. The source may be classified as unknown if there is insufficient evidence to classify the case as an importation or an importation-associated case despite identification of the genotype (Chapter 7. Molecular epidemiology of measles and rubella).
*Note: The requirement for verification of elimination has some subtle differences from the indicator for adequate molecular surveillance. For molecular surveillance, the indicator requires that a genotype should be identified for ≥80% of all chains of transmission. Refer to chapters 7 and 10 for additional information.