Emergence of Attenuated Measles Illness Among IgG-positive/IgM-negative Measles Cases: Victoria, Australia, 2008–2017

Abstract

Background Waning measles immunity among vaccinated individuals may result in an attenuated illness. This study compares the epidemiological, clinical, and laboratory profile of measles cases with waning immunity with other measles cases. Methods Polymerase chain reaction–positive (+) measles cases notified to Victoria’s Department of Health and Human Services from 2008 to 2017 with immunoglobulin (Ig) M and IgG tested at diagnosis were classified according to serology at diagnosis: IgG negative (−) (nonimmune), IgM+/IgG+ (indeterminate), or IgM−/IgG+ (waning immunity). Results Between 2008 and 2017, 297 measles cases were notified, of whom 190 (64%) were included; 151 of 190 (79%) were nonimmune at diagnosis, 26 (14%) were indeterminate, and 13 (7%) had waning immunity. Between 2008–2013 and 2014–2017, the proportion of cases with waning immunity increased from 0 of 87 (0%) to 13 of 103 (13%) (P < .001) and the diagnostic sensitivity of initial IgM fell from 93% to 81% (P = .012), respectively. Seven (54%) waning immunity cases reported receiving measles-containing vaccines; 1 case had 2 documented doses. Compared with nonimmune and indeterminate cases, waning immunity cases were more likely to be male; less likely to report fever, coryza, and cough; and had lower burden of virus (higher cycle threshold values). Waning immunity cases had higher IgG titers than indeterminate cases (mean optical density values, 1.96 vs 0.71; P = .004). Onward transmission from 1 waning immunity case was documented. Conclusions Waning immunity among measles cases, associated with secondary vaccine failure and modified clinical illness, is emerging in Victoria with transmission potential.

Measles Virus Infection and Immunity in a Suboptimal Vaccination Coverage Setting

“…Measles infections in vaccinated individuals are increasingly being reported when outbreaks occur in highly vaccinated populations [24][25][26][27][28][29][30][31][32][33][34][35][36]. Like for other cases reported in the literature [34,35,37], the symptoms were milder, and the viral RNA loads in body fluids were significantly lower than in measles-affected nonimmune individuals. Secondary vaccine failures were not associated with particular MeV genotypes, and sequencing of the MeV H gene did not identify any mutation in the epitopes of hemagglutinin recognized by neutralizing antibodies that could suggest the emergence of an escape mutant.…”

“…Pre-illness sera from twice-vaccinated measles cases were tested in an outbreak study in the Netherlands [51]. In that study, two out of four cases had levels of neutralizing antibodies below the estimated cutoff for clinical protection [37]. Finally, virus neutralization and cross-neutralization in the laboratory setting might not correspond to protection in vivo, even though immunological correlates of protection have been defined from clinical studies [44].…”

Application of a fast and cost-effective ‘three-in-one’ MMR ELISA as a tool for surveying anti-MMR humoral immunity: the Hungarian experience

“…These data raise the question concerning the reliability of the Hungarian population's herd immunity. Because of recent outbreaks worldwide, not only of measles, but also mumps and rubella (MMR) infections [15][16][17][18][19], and because of waning of immunity over time after vaccination [20][21][22][23], there is an urgent need for reliable and affordable laboratory tests for monitoring anti-MMR antibody (IgG) titres. For this purpose, we developed a new, 'three-in-one' immunoassay for quick measurement of all three anti-viral antibodies within a single run.…”

The Brief Case: Secondary Measles and the Pitfalls of Diagnostic Testing

“…However, measles cases still occur in the United States when the virus is introduced by travelers returning from parts of the world where measles is circulating, and outbreaks can occur in communities with larger numbers of unvaccinated persons. While the majority of cases are primary infections in persons who have not been vaccinated, measles can also occur in previously vaccinated individuals (1)(2)(3).…”

“…In addition, since the diagnosis of measles is often first considered with the onset of a rash, the IgG is often very high in a patient with secondary vaccine failure, due to an anamnestic immune response. Although IgM-negative/IgG-positive measles cases were previously reported and appear to be increasing (2-4), many clinicians, including infectious disease specialists, are unaware of the significance of this serologic pattern and of the critical importance of obtaining a nasopharyngeal (NP) or throat swab for RT-PCR (3,5).…”