Timing of development of measles-specific immunoglobulin M and G after primary measles vaccination

Abstract

A standard method for diagnosing measles is to detect measles-specific immunoglobulin M (IgM) in the serum of infected persons. Interpreting a positive IgM result from a person with suspected measles can be difficult if the person has recently received a measles vaccine. We have previously demonstrated that measles-specific IgM may persist for at least 8 weeks after primary vaccination, but it is unknown how quickly IgM appears. This study determined the timing of the rise of measles-specific IgM and IgG after primary measles vaccination with Schwartz vaccine. Two hundred eighty 9-month-old children from Ethiopia presenting for routine measles vaccination were enrolled. Sera were collected before and either 1, 2, 3, or 4 weeks after vaccination and tested for measles-specific antibodies by an IgM capture enzyme immunoassay (EIA) and by an indirect IgG EIA. A total of 209 of the 224 children who returned for the second visit had prevaccination sera that were both IgM and IgG negative. The postvaccination IgM positivity rates for these 209 children were 2% at 1 week, 61% at 2 weeks, 79% at 3 weeks, and 60% at 4 weeks. The postvaccination IgG positivity rates were 0% at 1 week, 14% at 2 weeks, 81% at 3 weeks, and 85% at 4 weeks. We conclude that an IgM-positive result obtained by this antibody capture EIA is difficult to interpret if serum is collected between 8 days and 8 weeks after vaccination; in this situation, the diagnosis of measles should be based on an epidemiologic linkage to a confirmed case or on the detection of wild-type measles virus.

FIG. 1

(a) Difference in IgM optical densities of positive and negative (P − N) wells for each infant by week after measles vaccination. The larger dashed line represents the 50th percentile for each week (a week was defined as a multiple of 7 ± 3 days; e.g., week 2 = 11 to 17). The horizontal dashed line represents the cutoff P − N value of 0.10, which was used in combination with the P/N ratio to determine whether the specimen was considered IgM positive, IgM borderline, or IgM negative. (b) Difference in IgG optical densities of P − N wells for each infant by week after vaccination. As in panel a, the larger dashed line represents the 50th percentile for each week, and the horizontal dashed line represents the cutoff P − N value of 0.09. Both graphs include only data for infants who were both IgM and IgG negative before vaccination.