Sex: U
Vaccine: MMR
Symptoms: Rash
Clinical narrative: Information has been received from a published literature article concerning a measles IgG avidity assay for use in classification of measles vaccine failure in measles elimination settings. Traditionally, measles IgG avidity assays have been used to clarify primary (PVF) and secondary (SVF) vaccine failures. PVF are vaccinated individuals who never responded to the vaccine and present with classic measles upon measles virus infection. In serum collected within 4 weeks of rash onset, measles IgM is present and measles IgG is of low avidity. Low-avidity results classify PVF and help confirm suspect cases even with a record of prior vaccination. In contrast, SVF are individuals with documented IgG antibody responses to vaccination whose antibody has waned over time, making them susceptible to measles virus infection. SVF produce high-avidity antibodies upon challenge with measles virus. High-avidity results classify SVF and can be used to verify secondary immune responses in modified-measles cases with elevated plaque reduction neutralization (PRN) titers (> 30,000 mlU/ml), a newly proposed biomarker to confirm SVF that otherwise would not be confirmed by routine serology or molecular-based tests. A well-validated measles avidity assay is needed for use as a complement to IgM testing in the serological confirmation of clinically ambiguous cases and to aid in the classification of measles vaccine failures. This study describes the development, evaluation, and applicability of a measles avidity assay. A commercially available measles IgG enzyme immunoassay was adapted for wider use. This case concerns 20 cases that patients experienced rash post-vaccination (>1 year). Samples from healthy adults exposed to measles virus infection or vaccination more than a year before collection were assumed to have high-avidity antibodies. Samples collected within 3 months after measles rash onset or first-time vaccination from IgM-positive children aged 9 months and older (to avoid maternal antibody interference) were expected to have results showing low- and intermediate-avidity antibodies, depending on the timing of sample collection. IgM was detected using the CDC measles capture IgM enzyme immunoassay. A total of 319 serum samples were retrospectively gathered from specimen collections acquired from diverse locations in the years 1988 to 2004 and archived at the author's institution. Institutional review board approval was obtained for outbreak and vaccine study samples. Specimens were also obtained from blood donated by healthy individuals under a CDC Institutional Review Board-approved protocol and from individuals in outbreaks who previously had natural measles or had received at least one dose of measles vaccine. The samples were distributed into group A and group B. Assumptions made for samples with uncertain epidemiological information (group B). Samples for Receiver operating characteristic curve (ROC) analysis were distributed into two groups: (i) a recent-exposure group with samples described as recent-exposure group (samples collected at 0 to 3 weeks were used to select the low-avidity threshold, and samples collected at 0 to 18 weeks were used to select for high-avidity threshold) and (ii) a distant-exposure group with samples described as collected 0 to 50 days after onset of rash, was used to select both avidity thresholds. Assumptions were made to use samples with uncertain epidemiological information. There are 20 cases of vaccinated with symptoms (characteristic>1 year) in the distant-exposure group. In conclusion, this paper introduces a new measles avidity assay that is ready to be used in elimination settings. It is highly accurate, precise, and reproducible, as well as sensitive and specific. The assay is able to detect measles-specific antibody maturation over time, in line with previous observations. Besides vaccine failure classification, avidity testing can provide very valuable information in confirming those cases with RT-PCR-negative results or with questionable IgM results. It must be emphasized that the assay can only be used to help rule in measles cases, but not to rule them out. With appropriate assay evaluation, it may be possible to adapt other commercially available measles IgG platforms to avidity testing by using the DEA elution method presented here. This avidity method worked well with another commercial plate coated with whole measles virus antigen (data not shown). Finally, the endpoint titration method was used because it is independent of the IgG concentration and it is considered superior to the single-dilution method. However, in situations where time or resources are limited, the avidity assay could be performed using a single dilution. This is one of several reports received from the same source (linked with Case# 1211USA012537). Additional information has been requested.