Abstract
In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from breakthrough infections was identified. Our results indicate that a high risk of onward transmission is limited to naïve infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.
Highlights
The 2-dose regime of measles vaccination has greatly reduced the morbidity and mortality of measles [1,2]
A confirmed breakthrough infection was defined as a case of confirmed measles with high-avidity IgG antibodies in acute serum according to criteria from the World Health Organization (WHO) Global Measles and Rubella Laboratory Network [22]
B: breakthrough infection; C: cough; EU: European Union; F: fever; K: conjunctivitis; N: naïve infection; ND: not done; R: rash; Z: coryza. a Breakthrough infection was defined as a confirmed case of measles in an individual with history of vaccination and/or positive IgG levels
Summary
The 2-dose regime of measles vaccination has greatly reduced the morbidity and mortality of measles [1,2]. In areas with high vaccination coverage, it has been estimated that the majority of cases in an outbreak will be breakthrough infections (i.e. infections in individuals with a history of vaccination) [11,12]. Transmission of infection from individuals with breakthrough infections seems to be rare [10,13,14,15], and the recently published national measles guidelines by Public Health England recommend only limited contact tracing around such cases [16]. Measles-specific IgG antibody titres are usually high in acute-phase serum but IgM may be undetectable, making analysis of measles virus RNA by real-time PCR the preferred diagnostic method for breakthrough infections [17,18]. Analysis of measles IgG antibody avidity or measles neutralising antibodies by plaque reduction neutralisation assays (PRN) in acute serum samples are used to confirm breakthrough infections [10,15,19,20]
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