Because symptoms can be mild, measles reinfection cases are often only recognized during investigations of individuals who had contact with a confirmed measles case. A high intensity of exposure (force of infection) is thought to play an important role in the occurrence of measles reinfection cases. Prolonged exposure to an acutely ill, confirmed case of measles in a medical setting has resulted in several reports of measles reinfections among health care workers [7,10,14,15].
Measles reinfection cases may have a history of one or two doses of MCV, and some cases have occurred in older individuals who claim to be unvaccinated [8]. The clinical presentation varies widely; a reinfection can be indistinguishable from a primary infection or may present with milder disease and modified symptoms. The initial site for the appearance of rash may be the trunk and arms rather than the face. The rash may not follow the usual progression or result in a full body rash. Similarly, the fever is generally less severe in an individual with a measles reinfection compared to a primary measles infection and cough, conjunctivitis and/or coryza, if present at all, are mild. If typical signs and symptoms of measles are present, they often resolve quickly.
Measles-specific IgG antibody in acute phase serum from measles reinfection cases is typically highly reactive (‘high’ positive) by EIA while IgM detection can vary. Depending on the sensitivity of the IgM assay, the IgM result may fall in the low positive or equivocal range. There may also be no detectable IgM in serum collected from measles reinfection cases. Therefore, detection of measles-specific RNA in appropriate clinical samples by RT-PCR is the best method to confirm a measles reinfection [16,17]. While it is not necessary to identify a reinfection case as such when there is a positive RT-PCR result, the occurrence of these cases can be documented by testing the avidity of the measles-specific IgG in acute serum [5]. Measurement of high avidity, virus-specific IgG is consistent with a prior immunologic response to measles from either vaccination or natural disease [5,8].
RT-PCR is the best method to confirm a measles reinfection; however, the window for RNA detection from measles reinfection cases may be shorter than for a primary case of measles [7,8,10]. Virologic specimens should be collected as soon as possible after rash onset to increase the likelihood of RNA detection. The paucity of reports that document secondary cases attributed to contact with measles reinfection cases may be due to the elevated and rapid production of neutralizing antibody that quickly reduces the viral load in these patients. The absence of a cough (or a mild, unproductive cough) also reduces the likelihood of effective transmission of infectious virus.
High levels of neutralizing antibody (IgG) may be present in serum specimens collected as soon as the first day of rash from measles reinfection cases. Because of the rapid rise in IgG, a rise in titre may not be apparent when testing conventionally-timed paired serum specimens, as discussed in 8.4 Additional testing to aid case classification.
However, exceptionally high titres may be observed in the first serum specimen (or both specimens). A threshold concentration of measles neutralizing antibody of ≥40,000 mIU/mL in a single serum specimen, as measured by the plaque reduction neutralization (PRN) assay [18], was demonstrated to identify and confirm a measles reinfection with 100% specificity [9]. Remarkably high levels of neutralising antibody titres measured by PRN from outbreaks involving previously vaccinated individuals with confirmed measles and high avidity IgG have also been reported [7-10]. The concentration of measles neutralizing antibody among some confirmed reinfection cases was >200,000 mIU/mL from serum specimens collected as early as 4 days after rash onset [8,9].
In a study of reinfection cases, remarkably high levels of neutralizing antibody were measured from most reinfection cases, but eight individuals (14%) produced much lower levels of antibody [9]. The eight confirmed reinfection cases had titres measured at 402 -29,367 mIU/ml in serum specimens that were collected at comparable intervals post rash onset as those collected from the reinfection cases with neutralising antibody titres ≥40,000 mIU/ml.
Because the PRN assay is rarely performed outside of a GSL, measurement of high avidity measles IgG antibody and detection of measles-specific RNA by RT-PCR is the best method to identify a reinfection case. It may be possible that end-point IgG antibody titres determined by serial dilutions of serum tested by EIA could be correlated with the level of measles neutralizing antibody titres measured by PRN that provide confirmation for a measles reinfection case. However, demonstration of a threshold end-point dilution level for IgG measured in an EIA that identifies a measles reinfection case has not been described.