Measles diagnostics in the elimination setting / L’anàlisi diagnòstica del xarampió en el marc de l’eliminació del virus del xarampió endèmic

Resumen

In regions where endemic measles virus circulation has been interrupted, laboratory confirmation of measles is like puzzle solving. The complexity of these puzzles depends on the available pieces of clinical, epidemiological and laboratory information. The main goal of this dissertation is to evaluate diagnostic laboratory tools to aid in suspected case confirmation in these settings. First, protocols to elute measles IgM and IgG antibodies from blood spots dried onto filter paper were compared to propose one that will permit the recovery of the maximum volume of eluted sample in the minimum time, effort and cost. An easy-to-implement protocol is proposed for the rapid extraction of serum for measles/rubella serology in outbreak situations for use in the World Health Organization Global Measles and Rubella Laboratory Network. Second, due to inherent limitations of measles specific IgM enzyme immunoassays and molecular methods used for measles confirmation, not all suspected cases can be resolved. For example, IgM and RNA may not be detected in vaccinated cases with waning immunity (secondary vaccine failures) and presenting with modified measles. The observation is made that serological parameters of elevated titers of high avidity neutralizing antibodies correlate with measles secondary vaccines failures and may be useful biomarkers for confirming secondary vaccine failures that cannot be confirmed otherwise. Third, a highly accurate measles IgG avidity enzyme immunoassay for vaccine failure classification is described. Detection of low avidity antibodies using this highly sensitive and specific avidity assay can complement existing measles diagnostic tools in confirming suspected cases when routine IgM testing may be inconclusive. Therefore, these diagnostic approaches can provide additional laboratory information to resolve suspected cases irrespective of vaccination status. Together, data presented in this dissertation may assist in enhancing measles control and surveillance in elimination settings.