Self-collected buccal swabs and rapid, real-time PCR during a large measles outbreak in Wales: Evidence for the protective effect of prior MMR immunisation

Moore, Catherine; Cottrell, Simon; Hoffmann, Jörg; Carr, Michael J.; Evans, Hannah; Dunford, Linda; Lawson, Heather; Brown, Kevin E.; Jones, Rachel

doi:10.1016/j.jcv.2015.03.012

Cited by 12 publications

(9 citation statements)

References 23 publications

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“…Measles vaccine combined with rubella, mumps and possibly varicella will probably meet a bigger acceptance in the population. More sentinel programmes of laboratory immunity checks should be established to discover gaps in herd immunity as early as possible [ 36 ]. If we succeed in increasing the acceptance of the measles vaccination and the awareness of the risks of MeV infections in our population, we really could—with the assistance of the effective combined vaccines—approach the major goal of regional measles elimination/worldwide eradication.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, they can still be neutralised by anti-H antisera without significant restriction, indicating that the vaccines are still fully effective [ 30 , 31 ]. The vast majority of measles patients in current outbreaks had not or not been sufficiently vaccinated, especially in terms of the second dose [ 10 , 35 , 36 ]. Are the current vaccination programmes appropriate?…”

Section: Challengesmentioning

confidence: 99%

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Eradication of measles: remaining challenges

Holzmann

Hengel²,

Tenbusch

et al. 2016

Med Microbiol Immunol

111

113

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Measles virus (MeV) is an aerosol-borne and one of the most contagious pathogenic viruses known. Almost every MeV infection becomes clinically manifest and can lead to serious and even fatal complications, especially under conditions of malnutrition in developing countries, where still 115,000 to 160,000 patients die from measles every year. There is no specific antiviral treatment. In addition, MeV infections cause long-lasting memory B and T cell impairment, predisposing people susceptible to opportunistic infections for years. A rare, but fatal long-term consequence of measles is subacute sclerosing panencephalitis. Fifteen years ago (2001), WHO has launched a programme to eliminate measles by a worldwide vaccination strategy. This is promising, because MeV is a human-specific morbillivirus (i.e. without relevant animal reservoir), safe and potent vaccine viruses are sufficiently produced since decades for common application, and millions of vaccine doses have been used globally without any indications of safety and efficacy issues. Though the prevalence of wild-type MeV infection has decreased by >90 % in Europe, measles is still not eliminated and has even re-emerged with recurrent outbreaks in developed countries, in which effective vaccination programmes had been installed for decades. Here, we discuss the crucial factors for a worldwide elimination of MeV: (1) efficacy of current vaccines, (2) the extremely high contagiosity of MeV demanding a >95 % vaccination rate based on two doses to avoid primary vaccine failure as well as the installation of catch-up vaccination programmes to fill immunity gaps and to achieve herd immunity, (3) the implications of sporadic cases of secondary vaccine failure, (4) organisation, acceptance and drawbacks of modern vaccination campaigns, (5) waning public attention to measles, but increasing concerns from vaccine-associated adverse reactions in societies with high socio-economic standards and (6) clinical, epidemiological and virological surveillance by the use of modern laboratory diagnostics and reporting systems. By consequent implementation of carefully designed epidemiologic and prophylactic measures, it should be possible to eradicate MeV globally out of mankind, as the closely related morbillivirus of rinderpest could be successfully eliminated out of the cattle on a global scale.

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Section: Discussionmentioning

confidence: 99%

Section: Challengesmentioning

confidence: 99%

Eradication of measles: remaining challenges

Holzmann

Hengel²,

Tenbusch

et al. 2016

Med Microbiol Immunol

111

113

View full text Add to dashboard Cite

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“…Although clinical descriptions were not routinely collected, many of the RICs included in the present study were described as having mild symptoms and/or a nonclassic presentation of rash. There is evidence to suggest that individuals with a reinfection are less likely to transmit virus than a primary case of measles ( 18 – 20 ). However, approximately 10% of the RICs in this study were identified as the source of infection of another case.…”

Section: Discussionmentioning

confidence: 99%

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

Sowers

Rota

Hickman

et al. 2016

Clin Vaccine Immunol

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In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml.

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“…In the United Kingdom (UK), endemic transmission of MeV was interrupted between 1995 and 2001 [ 14 ]. However, following a decrease in vaccination coverage, the number of confirmed measles cases has increased and several outbreaks have since been described in susceptible populations [ 15 – 19 ]. In England, measles surveillance is carried out at the Virus Reference Department of Public Health England (PHE).…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Utility of Whole Genome Sequencing of Measles Virus in the Characterisation of Outbreaks

et al. 2015

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BackgroundMeasles is a highly infectious disease caused by measles virus (MeV). Despite the availability of a safe and cost-effective vaccine, measles is one of the world-leading causes of death in young children. Within Europe, there is a target for eliminating endemic measles in 2015, with molecular epidemiology required on 80% of cases for inclusion/exclusion of outbreak transmission chains. Currently, MeV is genotyped on the basis of a 450 nucleotide region of the nucleoprotein gene (N-450) and the hemagglutinin gene (H). However, this is not sufficiently informative for distinguishing endemic from imported MeV. We have developed an amplicon-based method for obtaining whole genome sequences (WGS) using NGS or Sanger methodologies from cell culture isolates or oral fluid specimens, and have sequenced over 60 samples, including 42 from the 2012 outbreak in the UK.ResultsOverall, NGS coverage was over 90% for approximately 71% of the samples tested. Analysis of 32 WGS excluding 3’ and 5’ termini (WGS-t) obtained from the outbreak indicates that the single nucleotide difference found between the two major groups of N-450 sequences detected during the outbreak is most likely a result of stochastic viral mutation during endemic transmission rather than of multiple importation events: earlier strains appear to have evolved into two distinct strain clusters in 2013, one containing strains with both outbreak-associated N-450 sequences. Additionally, phylogenetic analysis of each genomic region of MeV for the strains in this study suggests that the most information is acquired from the non-coding region located between the matrix and fusion protein genes (M/F NCR) and the N-450 genotyping sequence, an observation supported by entropy analysis across genotypes.ConclusionsWe suggest that both M/F NCR and WGS-t could be used to complement the information from classical epidemiology and N-450 sequencing to address specific questions in the context of measles elimination.

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Self-collected buccal swabs and rapid, real-time PCR during a large measles outbreak in Wales: Evidence for the protective effect of prior MMR immunisation

Cited by 12 publications

References 23 publications

Eradication of measles: remaining challenges

Eradication of measles: remaining challenges

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

Assessment of the Utility of Whole Genome Sequencing of Measles Virus in the Characterisation of Outbreaks

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