Jrsm Open 2014_ p1

Clinical Review

A short clinical review of vaccination against measles

Leen Khader Tannous1, Gavin Barlow1,2 and Neil H Metcalfe31Hull York Medical School, YO10 5DD, York, UK2Department of Infection, Hull And East Yorkshire Hospitals NHS Trust3General Practitioner, North Yorkshire

Corresponding author: Leen Khader Tannous. Email: [email protected]

Summary

Major epidemics of measles are again in the news across

the UK because of our failure to maintain population herd

immunity. This situation has occurred primarily because of

a loss of public confidence in the measles, mumps and

rubella (MMR) vaccine, which was never restored following

the Wakefield debacle, and a lack of awareness of the

potential morbidity and mortality associated with measles.

This article provides healthcare professionals with a suc-

cinct overview of important clinical aspects of measles and

also describes the history of measles vaccination in the UK.

Restoration of herd immunity will require higher public

acceptance of the MMR vaccine in the context of recogni-

tion that measles remains an important infection. While

achievement of this appears to be challenging, recent

UK-based research suggests that it can be ascertained.

Keywordsmeasles, vaccine, vaccination

Introduction

Vaccination can be viewed in two dierent ways:one, as a supreme healthcare intervention thatcost-eectively reduces morbidity and mortality,or, two, as an unusual pattern of exposure wherethe route, dose, age of exposure and strain of virusthe person is exposed to, are all changed.1

Regardless of how individuals view vaccination,measles is one of the leading vaccine-preventablecauses of morbidity and mortality among youngchildren globally2 and is an important target forpublic health intervention. Recent, highly publicizedoutbreaks of measles in the UK have highlighted theneed for all healthcare professionals working in pri-mary and secondary care, and in public health, tobe aware of this re-emerging infection. In this con-cise article, we review key clinical aspects of measlesand place the current epidemiology of measles in theUK in the context of the turbulent history of mea-sles vaccine.

Methodology

We performed a literature review of English-languagestudies by searching the Medline and Cochrane col-laboration databases using the terms Measles,Vaccine, Eradication and History. Informationabout measles was also ascertained from the WorldHealth Organization (WHO), Health ProtectionAgency and the Medical Research Council (MRC)websites, and from general internet searches.

Important clinical aspects of measles

Measles is a disease caused by a single-stranded,negative-sense RNA Morbillivirus that is spread pri-marily via respiratory droplets with an incubationperiod of 814 days2; a high proportion of susceptiblehousehold contacts will develop infection. It is recog-nisable by the typical maculopapular rash associatedwith fever and the three Cs: cough, coryza and con-junctivitis, although not all of these may be presentand the rash can sometimes look atypical. The rashlasts for at least 3 days and is rst seen on the fore-head and neck, followed by the trunk and nally thelimbs. Patients are considered to be infectious untilafter the fourth day of rash. One of the signicantsequelae of measles infection is immunosuppression,which persists for a few weeks and increases the riskof secondary complications. Complications of mea-sles include otitis media (5%), respiratory tract infec-tions (4%), convulsions (0.5%) and neurologicalcomplications (0.1%)3 with immunocompromisedpatients, pregnant women and children less than1 year of age particularly at risk; susceptible individ-uals in these groups should be considered for humannormal immunoglobulin following exposure to mea-sles. Treatment is predominantly supportive, butantibiotics may be required in some cases for second-ary bacterial infection and high-dose vitamin Ashould be prescribed in those at risk of deciency.4

!2014 The Author(s)This is an open-access article distributed under the terms of the Creative Commons Non-commercial Attribution License (http://creativecommons.org/licenses/by-nc/2.0/),

which permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.

Journal of the Royal Society of Medicine Open;

5(4) 16

DOI: 10.1177/2054270414523408

at YildizTeknik Univ on December 23, 2014shr.sagepub.comDownloaded from

In the UK, cases should be reported to the localhealth protection unit and when admitted to hospitalpatients should be isolated, preferably in a negativepressure isolation room, and the infection controlteam informed; susceptible healthcare sta shouldnot have contact with suspected cases. The potentialimpact of nosocomial transmission from a patient toa healthcare worker and onward to a second patientwas recently reported; 110 contacts were identied forthe healthcare worker with 61 advised to have vac-cination and 5 given immunoglobulin.5 As with inu-enza and other vaccine-preventable infections, toavoid such occurrences, healthcare organizationsand individual sta members have an ethical obliga-tion to be aware of and ensure maintenance of theirvaccination status.

Because the symptoms of measles are non-specic,and patients with fever and rash commonly present toboth primary and secondary care, cases are easilymissed. However, in a population that is subopti-mally vaccinated and suering outbreaks, as is thecase in the UK currently, to ultimately achieve eradi-cation, the identication of cases is critically import-ant to public health interventions, such as contacttracing and the immunization of susceptible individ-uals; coalface healthcare professionals thereforeneed a low threshold to considering measles a pos-sible diagnosis. The WHO denes a case as: anyperson in whom a clinician suspects measles, or anyperson with fever and generalized maculopapularrash and cough, coryza or conjunctivitis.4 The pres-ence of measles-specic IgM antibodies, in the appro-priate clinical context, provides laboratoryconrmation of a measles case. Awareness of the clin-ical symptoms and signs of measles among healthprofessionals in the UK is likely to be considerablylower than in previous decades, but is critical to redu-cing the number of missed cases and increasing inter-vention opportunities. Given that measles is anextremely contagious infectious disease with consid-erable morbidity, population vaccination is a criticalpart of prevention and control. The description of acase of measles in a young adult, with photographs ofthe rash, recently admitted to our unit is available viaopen access.6

The history of the measles vaccine

1950s1980s

Before the rst clinical use of measles vaccine in theUK, there were cycles of large epidemics every otheryear. The peak in 1955 saw 693,803 measles cases thatcontributed to 174 deaths (0.025%).7 The early use ofmeasles vaccines in 1961 was based on a trial of three

live attenuated vaccines derived from the Edmonstonstrain.8 Seventy-seven children took part in theresearch and although a protective antibody responsewas achieved, over half of the children experiencedmoderate to severe systemic reactions, including rash,pyrexia and tonsillitis.9 To reduce these side eects, aweaker vaccine strain was developed and tested bythe MRC in a series of four trials.10 The use of asingle antigen measles vaccine was subsequentlyintroduced in the UK for children between 1 and 2years of age in 1968. In the 1970s, there was poorvaccination coverage with fewer than 60% of childrenvaccinated by the age of 2 years.11 It was not until thelate 1970s that major national and internationaleorts developed routine immunization systems. Asa result, by the mid-1980s measles vaccination cover-age had increased to 80% with the number of casesdecreasing to less than 100,000 per year with 13deaths compared with peaks of over half a millioncases and 100 deaths in previous decades.12 Between1985 and 1988, however, vaccine failure remainedcommon. The reasons for this were described byKrugman,13 and included: inadequate refrigerationof vaccine, early administration (before 12 monthsof age), excessive exposure of vaccine to light, simul-taneous administration of gamma globulin and theuse of killed measles vaccine.

In 1988, a combined measles, mumps and rubella(MMR) vaccine replaced the single antigen vaccineand was given to children between 1 and 2 years ofage. It was also oered to preschool children over theage of two in a catch-up programme.11 As seen inFigure 1,14 following the introduction of MMR toseveral national vaccination campaigns and to theroutine childhood immunization programme, cover-age at 2 years of age reached a peak of around 92% in1991 persisting until 1998.

1990s

Although notications of measles fell annually from1988 to 1991, an increase occurred in older children in1992.11 A second dose of MMR at the age of 11 yearswas therefore introduced. Revaccination has beenshown to increase clinical protection from 95% to99.7%,11 which is important from the population per-spective considering that 9295% vaccination cover-age15 is needed to achieve herd immunity and protectunvaccinated, susceptible individuals. During thisperiod a failure in maintaining high vaccinationcoverage occurred leading to an epidemic in westernScotland and several outbreaks in England andWales.11 A combined measlesrubella vaccine was,therefore, oered to all schoolchildren aged 516years in a 6 week national campaign in 1994.11

2 Journal of the Royal Society of Medicine Open 5(4)


In 1993, Wakeeld et al.16 published an article sug-gesting a link between exposure to measles vaccinesand Crohns disease in children.

In 1996, a two-dose schedule of MMR was rou-tinely oered to all children, the rst dose given at1213 months with a booster between the age of 3years and 4 months and 5 years.11 In 1998, the nowinfamous research article by Wakeeld et al.17 waspublished in The Lancet. This erroneously suggesteda link between the MMR vaccine, bowel disease andautism. The research included 12 children, 8 of whomappeared to have developed the condition veryshortly after receiving MMR vaccine. The authorsrecommended the use of single vaccines instead ofthe combined MMR vaccine.15 This triggered imme-diate criticism and consequently a meeting of over 30experts, convened by the MRC, concluded that theevidence did not support a causal link betweenMMR, autism and bowel disease. It has also beensuggested18 that the research behind The Lancet art-icle was a sophisticated fraud. The lead author,Andrew Wakeeld, however, continues to defendhis position, although he has now been struck othe General Medical Council medical register in theUK.1 Numerous studies have subsequently failed toshow an association between MMR vaccine andautism.

In 1999, the publics response to Wakeelds paperresulted in a decline in vaccination coverage and anincrease in parental demand for single MMR vac-cines. The UK government subsequently banned the

single-dose vaccine, which was the only alternative toMMR. This decision was based on a number of rea-sons, including a failure to pass UK safety testing,delay in the complete immunisation of children,reduction in the percentage of children vaccinatedand an increase in the number of injections andpotential for side eects.19

2000 onwards

Given that the measles vaccine is as eective in thesingle formulation,2 it has been argued that keepingthe options of both MMR and single-dose vaccinesfor parents might have maintained higher populationcoverage and reduced the subsequent increase in mea-sles cases and outbreaks. It is likely, however, thatgovernment approved use of the single vaccinewould have further undermined the MMR vaccineand made subsequent re-introduction to the child-hood vaccination schedule more dicult for thepublic to accept. Although vaccination coverage inEngland was at its lowest in 20032004,14 the inci-dence of measles remained low. As Figure 2 shows,however, it began to rise sharply in 2008 and 2009, aspopulation herd immunity decreased.20

In early 2012, one of the largest outbreaks of mea-sles since 1988 occurred in Liverpool with 301 con-rmed and 148 probable cases21 resulting in anincrease in MMR uptake rates. Between Januaryand April 2012 there were 447 conrmed cases ofmeasles in England and Wales.22 MMR coverage at

Figure 1. MMR vaccine coverage in England at 2 years of age, 19881989 to 20102011 (based on HPA information).14

Tannous et al. 3


this time remained lower than in the mid-1990s andconsiderably lower than the WHO target of 95%required for adequate population protection.11

Subsequently, large and highly reported outbreaksin, for example, northeast England and south Waleshave occurred, the latter consisting of over 1000 caseswith 7% requiring hospital attendance; over 75,000vaccines were subsequently administered to unvaccin-ated individuals.23 Although targets set by theEuropean region of the WHO for the elimination ofmeasles from Europe could not be met in 2010, thetarget date was reset to 2015. However, as noted,there may be a considerable time lag between adecrease in vaccination coverage and a subsequentincrease in the number of cases, so in light of recentUK and European outbreaks it seems unlikely thatthe 2015 target will be achieved.

What can we learn from the history ofmeasles vaccination in the UK?

Perhaps the clearest message from the historydescribed is that when vaccine uptake is inadequateor falls, there is a predictable subsequent decline inherd immunity and an increase in the incidence ofmeasles. This eect may be delayed; the consequencesof Wakeelds erroneous research, published in 1998,have only been realized in recent years. The under-lying cause of this has been an ongoing underminingof the safety of MMR vaccine, particularly by someof the popular media, and a subsequent loss of public

condence. Although the reasons why people do notseek vaccination of themselves or their children areclearly complex, as demonstrated in a recent qualita-tive study,24 the high uptake of other childhood vac-cines without controversy, however, such asconjugate pneumococcal vaccine introduced in 2006after the problems with MMR, suggests that thepublic will accept vaccination. It appears that oncea vaccine scare story, even if subsequently thoroughlydiscredited, however, enters the publics mindset, it isa very challenging situation to reverse, the conse-quences of which can last for years and beyond asingle generation. A recent UK-based cluster-randomized controlled trial, however, showed thatweb-based decision support can signicantly reduceparental decision conict and was associated withhigh vaccine uptake.25

Although the recent high prole local outbreaks ofmeasles may start to reverse the publics scepticism ofthe MMR vaccine, any such eect is likely to be tem-porary and cannot be relied on long term. A recentmathematical modelling study showed the dangers ofdoing so and suggested a potential important feed-back loop between disease prevalence and vaccineuptake; when the infection is rare due to vaccination,public awareness of the consequence of infection islow, and the impact on vaccine uptake of any con-troversy is therefore disproportionately exaggerated;the publics incentive to get themselves or their chil-dren vaccinated is low.26 Whether other interven-tions, implemented before these outbreaks, could

Figure 2. All laboratory confirmed cases of measles in England and Wales, 19962011* (based on HPA information).20



have made a dierence is open to debate, but a recentUK-based quality improvement study clearly demon-strates that improvement in vaccine uptake is achiev-able in a deprived and diverse inner-city populationusing a complex intervention with componentsincluding geographically based networks of generalpractices, small nancial incentives, consistentcoding, a systematic call/recall system, and surveil-lance and feedback of performance.27

Conclusion

All coalface primary, secondary and public healthhealthcare professionals should have, at the veryleast, a basic understanding of measles infectionand the historical and contemporary issues surround-ing vaccination. High vaccine uptake remains the keycritical control point in achieving herd immunity anderadicating measles in the longer term. Increasingvaccination coverage is likely to be primarily depend-ent on public acceptance of the vaccine; educationand maintenance of public awareness of the import-ance of measles infection, in the context of innovativeand established interventions, are likely to be import-ant drivers of this. Healthcare providers should takeevery opportunity to reinforce the message thatMMR vaccine is safe, highly eective and the mainroute to reducing cases of measles and associatedmorbidity and mortality.

Key points for healthcare professionals

. Measles typically presents with a maculopapularrash, fever and the three Cs: cough, coryza andconjunctivitis

. Patients with suspected measles admitted to hos-pital should be isolated with susceptible healthcareworkers avoiding contact with such patients

. Healthcare workers have a responsibility to beaware of their vaccination status and to seek vac-cination if appropriate

. Rapid response to measles cases with reporting tolocal health protection units is vital in the publichealth response to cases

. Measles vaccine in the form of the MMR vaccineis safe and very eective; high uptake is the key toeliminating measles and healthcare professionalsand organizations should try to educate and main-tain public awareness of the importance of measles

Declarations

Competing interests: None declared

Funding: None declared

Guarantor: LKT

Ethical approval: Not required

Contributorship: All authors included in this paper full thecriteria of authorship and there is no one else who fulls the criteria

but has not been included as an author. In terms of contribution,

LT is responsible for the overall content as guarantor. GB and NM

were equally involved in the analysis and interpretation of data,

revising the article critically for important intellectual content and

the nal approval of the version to be published.

Acknowledgements: None

Provenance: Not commissioned; peer-reviewed by EmmanuelOkpo

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