Limitations of serological screening for measles immunity in young health care workers in New Zealand

Requirements for documentation of measles (Me) immunity in health care workers (HCWs) vary. At the University of Otago, New Zealand (NZ), student HCWs with or without two documented doses of Me-mumps (Mu) -rubella (Ru) (MMR) vaccine, are tested for Me, Mu, and Ru IgG by an indirect sandwich chemiluminescent immunoassay (CLIA) and receive a third dose of MMR (MMR3) if seronegative for Me, Mu, or Ru. We compared Me seropositivity by CLIA with two tests at the Netherlands Public Health Institute (RIVM): in-house bead-based multiplex immunoassay (MIA) and plaque reduction neutralization test (PRNT), using Me seropositivity thresholds of ≥16.5 Arbitrary Units (AU)/ml for CLIA and ≥ 0.12 International Units (IU)/ml for MIA and PRNT. Of 725 students, 175 (24.1 %) were below CLIA thresholds for ≥1 of Me, Mu, or Ru, and received MMR, with 88 (50.2 %) participating in the study. Seropositivity for Me by CLIA was significantly less common (43; 48.9 %; 95 % CI: 38.5, 59.4) than for MIA (80, 90.9 %; 95 % CI: 82.7, 95.4) or PRNT (74; 84.1 % (95 % CI, 74.8, 90.4). Among the 14 PRNT seronegatives, proportions of false positives by CLIA (4/43, 9.3 %) and MIA (7/80, 8.8 %) were similar. Among PRNT seropositives, the only MIA seronegative was in low positive (<0.24 IU/ml) range, whereas among CLIA seronegatives, 26/55 (47.2 %) had PRNT >0.24 IU/ml. Our finding that CLIA did not detect neutralizing antibody in a high proportion of vaccinated young adults agrees with other studies. In our study population, approximately 9 % of Me seropositives on both MIA and CLIA had PRNT <0.12 IU/ml. In elimination settings, non-PRNT serological tests have significant limitations in two-dose vaccinated HCWs, with implications for their use in screening to determine requirement for MMR3.