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350 WEEKLY EPIDEMIOLOGICAL RECORD, NO. 35, 28 AUGUST 2009

an estimated global total of >23 million disability-adjustedlife years were lost as a result of measles.1

Measles can be prevented readily by vaccination. In 2007,worldwide coverage of the rst dose of measles vaccinereached 82%; between 2000 and 2007, the estimated numberof deaths from measles dropped from 750 000 to 197 000. 2However, measles remains an important cause of death anddisability in countries with limited health infrastructure. In

countries where vaccination has substantially reduced theincidence of measles, failure to maintain high coverage ofchildhood immunization in all districts has resulted in aresurgence of the disease.

The pathogen and the diseaseMeasles virus (genus Morbillivirus, family Paramyxoviridae)is an enveloped, single-stranded RNA virus that has globallyretained its monotypic antigenic structure for decades. Thegenome encodes 8 proteins, including the haemagglutinin(H) and the fusion (F) proteins. The lifelong immunity thatfollows infection is attributed to neutralizing antibodiesagainst the H protein.3 Sequencing of the measles virus ge-nome has so far identied 23 different genotypes that canbe used to track transmission.4

Towards the end of the incubation period, patients developprodromal symptoms of high fever, cough, coryza and con-

junctivitis. The typical maculopapular rash appears afteranother 34 days, often accompanied by a fever that peaksat 3940 C. At the onset of rash, bluish-white Kopliks spots,which are pathognomonic of measles, are seen in the oralmucosa. Patients normally improve by the third day afterrash onset and are fully recovered 710 days after onset ofdisease.

The severity of measles varies widely, depending on a num-ber of host and environmental factors. The risk of develop-ing severe or fatal measles increases for those aged

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RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No35, 28 AOT 2009 353

receiving 1 dose of measles vaccine was 89.6% (interquartilerange, 8295%); the median proportion of infants vaccinatedaged 1112 months who seroconverted was 99% (inter-quartile range, 93100%). The development of a high avidityantibody response is critical to the development of protec-tive immunity to measles virus. Antibody avidity to measlesvirus is generally lower in children vaccinated at age 6months or 9 months compared with the avidity obtained inchildren vaccinated at age 12 months.

Studies on revaccination in children who failed to respondto their rst dose of measles vaccine show that almost alldevelop immunity after their second dose (median propor-tion, 97%; interquartile range, 87100%).9In people with pre-existing antibodies, revaccination may not result in sufcientviral replication to boost antibody concentrations. Althoughvaccine-induced antibody concentrations decline over timeand may become undetectable, immunological memory per-sists and, following exposure to measles virus, most peoplewho have been vaccinated produce a protective immuneresponse.

Vaccine effectiveness and duration of protectionThe worldwide impact of mass immunization on the inci-dence of measles has been well documented,13and numerouseld studies testify to the effectiveness of MCV. The provenbenet of the vaccine makes it unethical to withhold vac-cination in control groups, so randomized controlled trialsin this eld are scarce.14

Following vaccination, the long-term persistence of neutral-izing measles antibodies (2633 years) and long-lasting pro-tection against measles have been demonstrated by severalinvestigators. However, it is not denitively known whethera single dose of measles vaccine, without natural boostingby recurrent measles exposure, will result in lifelong protec-tion. Studies using IgG avidity measurements to separateprimary vaccination failures from secondary vaccinationfailures suggest that secondary failures may occur at least

occasionally.15, 16 On the other hand, a number of studies ofmeasles outbreaks in teaching institutions, as well as studiesfrom countries or isolated islands with resurgent outbreaks,have failed to identify declining immunity as an importantrisk factor.17

Delivery strategiesMeasles vaccination policy and delivery strategies vary con-siderably among countries. In the early years of the Ex-panded Programme on Immunization, the recommendationwas to administer only 1 dose of MCV. However, since pri-mary vaccination failure occurs in up to 1015% of infantsvaccinated at age 9 months, this strategy has proven insuf-cient to prevent measles outbreaks.

13 Strebel PM et al. Measles vaccine. In: Plotkin S, Orenstein W, Oft P, eds. Vaccines,5th ed. Philadelphia, Saunders Elsevier, 2008: 352398.

14 Grading of scientic evidence Table I (effectiveness) with key references. Availablefrom http://www.who.int/immunization/measles_grad_effectiveness.pdf

15 Paunio M et al. IgG avidity to distinguish secondary from primary measles vaccina-tion failures: prospects for a more effective global measles elimination strategy.Expert Opinion on Pharmacotherapy, 2003, 4:12151225.

16 Pannuti CS et al. Identication of primary and secondary measles vaccine failures bymeasurement of immunoglobulin G avidity in measles cases during the 1997 So

Paulo epidemic. Clinical and Diagnostic Laboratory Immunology, 2004, 11:119122.

17 Grading of scientic evidence Table II (duration of protection) with key references.Available from http://www.who.int/immunization/measles_grad_duration.pdf

a t de 89,6% (intervalle interquartile, 82-95%); de 11 12 mois, laproportion de sroconversions a t de 99% (intervalle interquartile,93-100%). Le dveloppement dune rponse par apparition danti-corps avidit leve est essentiel pour linstauration dune immunitprotectrice contre le virus de la rougeole. Lavidit des anticorps pourle virus rougeoleux est en gnral plus faible chez lenfant vaccinentre 6 et 9 mois par rapport celle obtenue chez les enfants 12 mois.

Les tudes sur la revaccination des enfants qui nont pas ragi lapremire dose du vaccin antirougeoleux montrent que presque tousont dvelopp une immunit la suite de la seconde dose (proportionmdiane, 97%; intervalle interquartile, 87-100%).9 Chez les sujetsayant des anticorps prexistants, la revaccination pourrait ne pasdonner une rplication virale sufsante pour stimuler les concentra-tions en anticorps. Bien que les titres en anticorps induits par lavaccination baissent avec le temps et peuvent devenir indtectables,la mmoire immunologique persiste et, aprs une exposition au virusde la rougeole, la plupart des personnes qui ont t vaccines produi-sent une rponse immunitaire protectrice.

Efficacit du vaccin et dure de la protectionOn a bien tabli limpact mondial de la vaccination de masse surlincidence de la rougeole13 et de nombreuses tudes sur le terrainattestent de lefcacit des vaccins antirougeoleux. Les avantagesavrs de ces vaccins font quil est contraire lthique de priver desgroupes tmoins de cette vaccination, de sorte que les essais contr-ls randomiss sont rares dans ce domaine.14

Plusieurs chercheurs ont mis en vidence la persistance des anticorpsantirougeoleux sur le long terme (26-33 ans) et la protection delongue dure confre par la vaccination. En revanche, on ne sait pasavec certitude si une dose unique du vaccin, sans rappel naturel pardes expositions rcurrentes la rougeole, assure une protection d-nitive tout au long de la vie. Les tudes reposant sur les mesures delavidit des IgG pour faire la distinction entre les checs de la vacci-nation primaire et ceux de la vaccination secondaire semblent indi-quer que des checs secondaires puissent se produire au moins occa-

sionnellement.15, 16 Dun autre ct, un certain nombre dtudes surdes ambes de rougeole dans des tablissements denseignement,ainsi que des tudes portant sur des pays ou des les isoles connais-sant des ambes rcurrentes, nont pas russi dnir la baisse delimmunit comme un facteur de risque important.17

Stratgies dadministrationLes politiques de vaccination contre la rougeole et les stratgies dad-ministration varient beaucoup dun pays lautre. Dans les premiresannes du Programme largi de Vaccination, il tait recommanddadministrer une seule dose de vaccin antirougeoleux. Mais, commela vaccination primaire choue dans une proportion pouvant attein-dre 10 15% des nourrissons gs de 9 mois, cette stratgie sestavre inefcace pour la prvention des ambes de rougeole.

13 Strebel PM et al. Measles vaccine. In: Plotkin S, Orenstein W, Oft P, eds. Vaccines, 5th ed. Phi-ladelphia, Saunders Elsevier, 2008: 352398.

14 Cotation des preuves scientiques Tableau I (efcacit) avec rfrences cl. Disponible surhttp://www.who.int/immunization/measles_grad_effectiveness.pdf

15 Paunio M et al. IgG avidity to distinguish secondary from primary measles vaccination failures:prospects for a more effective global measles elimination strategy. Expert Opinion on Pharma-cotherapy, 2003, 4:12151225.

16 Pannuti CS et al. Identication of primary and secondary measles vaccine failures by measure-ment of immunoglobulin G avidity in measles cases during the 1997 So Paulo epidemic.Clinical

and Diagnostic Laboratory Immunology, 2004, 11:119122.

17 Cotation des preuves scientiques Tableau II (dure de la protection) avec rfrences cl.Disponible sur http://www.who.int/immunization/measles_grad_duration.pdf

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As of 2008, a delivery strategy to offer 2 doses of measlesvaccine is used by 192 of 193 Member States: a total of132 countries use a routine 2-dose schedule; 49 of these alsoconduct regular, nationwide campaigns, often referred to assupplementary immunization activities (SIAs);1839 have con-ducted a 1-time catch-up campaign; and 44 rely only on thedelivery of 2 routine doses. A total of 60 countries use aroutine rst dose plus regular SIAs.

The timing of and delivery strategies for the rst dose ofMCV (MCV1) and the second dose (MCV2) varies acrosscountries and regions but, in general, countries with long-standing immunization programmes offer both doses at laterages and rely on routine services for delivery. Countries witha weaker health infrastructure use SIAs to deliver MCV2 be-cause these activities are specically targeted towards reach-ing children outside the health system. The diversity inmeasles immunization schedules results from differencesamong countries in rates of endemic measles transmission,the goals for measles control (such as mortality reductionversus the elimination of measles), the health-service infra-structure, as well as in the ability of programmes to accesschildren at different ages.

Earlier evidence suggested that SIAs initiated to interrupttransmission of the virus may not have had a substantialimpact on the course of outbreaks.19 However, recent stud-ies20have shown that, in some areas, immunization initiatedin response to outbreaks was associated with reduced mor-bidity and spread, particularly if immunization was startedearly, covered a wide age range and achieved high coverage.Revised WHO guidelines on responding to outbreaks areavailable.8

Equal protection against measles is achieved when measlesvaccine is used alone or in combined products, such asmeasles-rubella vaccine or MMR. Immunogenicity and reac-togenicity of the individual components are similar whenMCVs are administered as combined products or simultane-ously at different anatomical sites with other vaccines, such

as diphtheria toxoid, tetanus toxoid, pertussis vaccine, Hae-mophilus infuenzaetype b vaccine, poliovirus vaccines (oralpoliovirus vaccine [OPV] or inactivated poliovirus vaccine),varicella vaccine, hepatitis B vaccine, or heptavalent pneu-mococcal vaccine.21, 22 Similarly, available date suggest thatvaccines against measles and yellow fever or Japanese en-cephalitis may be administered at the same time at differ-ent sites.23However, as a modest reduction of the immuneresponse to measles vaccine has been observed, furtherinvestigation on the possible impact of co-administrationof Japanese encephalitis vaccine on measles vaccine effec-

18 The primary purpose of SIAs is to reach children who have been missed by routineservices. In general, there are 2 approaches. An initial, nationwide catch-up SIAtargets all children aged 9 months to 14 years; its goal is to eliminate susceptibility

to measles in the general population. Periodic follow-up SIAs then target all childrenborn since the last SIA. Follow-up SIAs are conducted nationwide every 24 yearsand target children aged 959 months; their goal is to eliminate any measles sus-ceptibility that has developed in recent birth cohorts.

19 WHO guidelines for epidemic preparedness and responses to measles outbreaks.Geneva, World Health Organization, 1999 (WHO/CDS/CSR/ISR/99.1).

20 Grais RF et al. Exploring the time to intervene with a reactive mass vaccinationcampaign in measles epidemics. Epidemiology and Infection, 2006,134:15.

21 Zepp F et al. Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine co-administered with a booster dose of a combined diphtheria-te-tanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus infuenzaetype b conjugate vaccine in healthy children aged 1223 months. European Journalof Pediatrics, 2007, 166:857864.

22 Black SB et al. Immunogenicity and safety of measles-mumps-rubella, varicella andHaemophilus infuenzaetype b vaccines administered concurrently with a fourthdose of heptavalent pneumococcal conjugate vaccine compared with the vaccinesadministered without heptavalent pneumococcal conjugate vaccine.Pediatric Infec-

tious Disease Journal, 2006, 25:306311.23 Gatchalian S et al. Comparison of the immunogenicity and safety of measles vaccine

administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vac-cine in Philippine infants. Vaccine, 2008, 26:22342241.

En 2008, 192 tats Membres sur 193 appliquaient une stratgie dadmi-nistration de 2 doses vaccinales: 132 utilisaient un calendrier de vacci-nation systmatique prvoyant les 2 doses, 49 dentre organisant rgu-lirement des campagnes nationales de vaccination, appeles courammentactivits de vaccination supplmentaires (AVS);18 39 ont organis unecampagne unique de rattrapage; 44 ne comptaient que sur ladministra-tion systmatique de 2 doses. Au total, 60 pays administraient la premiredose en routine et organisaient en plus rgulirement des AVS.

Le calendrier et la stratgie dadministration de la premire dose etde la seconde dose de vaccin antirougeoleux varient dun pays et dunergion lautre mais, en gnral, les pays disposant depuis longtempsde programmes de vaccination, proposent les 2 doses un ge plustardif et sappuient sur les services de vaccination systmatique. Lors-que les infrastructures de sant sont moins solides, les pays ont recoursaux AVS pour ladministration de la seconde dose, parce que ces acti-vits ciblent spciquement les enfants en dehors du systme de sant.La diversit des calendriers de la vaccination antirougeoleuse provientdes diffrences entre les pays au niveau des taux de transmission dela rougeole endmique, des buts de la lutte contre cette maladie (parexemple diminution de la mortalit ou limination de la rougeole), desinfrastructures des services de sant, ainsi que de la capacit desprogrammes de voir les enfants des ges diffrents.

Selon des indications antrieures, les AVS organises pour interrom-pre la transmission du virus pourraient ne pas avoir deffet sensiblesur lvolution des ambes.19 Toutefois, des tudes rcentes20 ontmontr que, dans certaines rgions, les vaccinations entreprises lasuite de ambes se sont associes une rduction de la morbiditet de la propagation, en particulier si les vaccinations ont commencrapidement, ont couvert une tranche dge tendue et ont eu unecouverture leve. La rvision des lignes directrices de lOMS pourla rponse aux ambes est disponible.8

Que le vaccin antirougeoleux soit administr seul ou en association, avecla rubole ou avec les oreillons et la rubole (ROR) par exemple, onobtient une protection quivalente. Limmunognicit et la ractognicitdes lments individuels sont les mmes que les vaccins antirougeoleuxsoient administrs seuls, en association ou que lon administre simulta-nment sur plusieurs sites anatomiques plusieurs autres vaccins, comme

lanatoxine diphtrique, lanatoxine ttanique, le vaccin contre la coque-luche, le vaccin anti-Haemophilus infuenzae type b, les vaccins contrela poliomylite (vaccin antipoliomylitique buccal [VPO] ou vaccin inac-tiv), contre la varicelle, lhpatite B ou le vaccin heptavalent anti-pneu-mocoque.21, 22De mme, les informations disponibles suggrent queles vaccins contre la rougeole, la vre jaune et lencphalite japo-naise soient administrs simultanment sur des sites diffrents.23Toutefois, vu quon a observ une lgre diminution de la rponseimmunitaire au vaccin antiougeoleux, une enqute plus poussesur limpact possible dune co-administration du vaccin contrelencphalite japonaise sur lefcacit du vaccin contre la rougeole

18 Les AVS ont pour but principal de vacciner les enfants qui nont pas bnci de la vaccinationsystmatique. On applique en gnral 2 mthodes. Une AVS initiale nationale de rattrapage vise vacciner tous les enfants de 9 mois 14 ans et elle a pour but dliminer la sensibilit la

rougeole dans lensemble de la population. Des AVS rgulires de suivi ciblent ensuite tous lesenfants ns depuis la dernire AVS. Elles sont organises lchelon national tous les 2 4 anset visent les enfants gs de 9 59 mois, leur but tant alors dliminer la sensibilit la rou-geole apparue dans les dernires cohortes de naissances.

19 WHO guidelines for epidemic preparedness and responses to measles outbreaks. Genve, Orga-nisation mondiale de la Sant, 1999 (WHO/CDS/CSR/ISR/99.1).

20 Grais RF et al. Exploring the time to intervene with a reactive mass vaccination campaign inmeasles epidemics. Epidemiology and Infection, 2006,134:15.

21 Zepp F et al. Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vac-cine co-administered with a booster dose of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus infuenzaetype b conjugate vaccine in healthychildren aged 1223 months. European Journal of Pediatrics, 2007, 166:857864.

22 Black SB et al. Immunogenicity and safety of measles-mumps-rubella, varicella and Haemophi-lus infuenzaetype b vaccines administered concurrently with a fourth dose of heptavalentpneumococcal conjugate vaccine compared with the vaccines administered without heptavalentpneumococcal conjugate vaccine. Pediatric Infectious Disease Journal, 2006, 25:306311.

23 Gatchalian S et al. Comparison of the immunogenicity and safety of measles vaccine administe-red alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants.Vaccine, 2008, 26:22342241.

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tiveness is encouraged.24 As a general rule, live vaccinesshould be given either simultaneously or at intervals of4 weeks. An exception to this rule is OPV, which can be givenat any time before or after measles vaccination without in-terference in the response to either vaccine.

Measles vaccination and HIVA systematic review and meta-analysis of the safety and im-

munogenicity of measles vaccine in HIV-infected children wasrecently commissioned by WHOs Global Advisory Committeeon Vaccine Safety (GACVS).25 The analysis did not show anincreased risk of serious adverse events among HIV-positivechildren when compared with uninfected children. Serologicalassessment of measles antibody titres after vaccinationshowed that measles vaccination at age 6 months resulted insimilar levels of protection in HIV-infected children and inchildren who had not been exposed to HIV (combined relativerisk [RR] 1.05; 95% condence interval [CI], 0.831.34; hetero-geneity I2, 65.7%; P=0.054).26 By age 9 months, fewer HIV-in-fected children (with or without clinical signs of AIDS) re-sponded to measles vaccine than did children who had notbeen exposed to HIV (combined RR, 0.79; 95% CI, 0.611.02;heterogeneity I2, 81.5%; P=0.005). Two studies suggested that

the antibody response in HIV-infected children waned fasterthan in children who were not infected. There were scant dataabout the effects of highly active antiretroviral therapy (knownas HAART) on responses to measles vaccination and limitedpossibilities to compare vaccinated children to unvaccinatedHIV-infected children. Data on clinical effectiveness were alsoscarce. Based on this review, GACVS found no evidence tosupport changes to WHOs recommendations to immunizeasymptomatic HIV-infected children.27, 28

Adverse reactionsAdverse reactions following measles vaccination are gener-ally mild and transient.29, 30Slight pain and tenderness at thesite of injection may occur within 24 hours; this is some-times followed by a mild fever and local adenopathy. About712 days after vaccination, up to 5% may experience feverof at least 39.4 C for 12 days. The fever occasionally inducesfebrile seizures (in about 1/3000 people). A transient rashoccurs in about 2%; thrombocytopenic purpura occurs inapproximately 1/30 000 people who are vaccinated.31, 32 Ad-verse events, with the exception of anaphylactic reactions,are less likely to occur after receipt of MCV2.

Allergic reactions to vaccine components, including neomy-cin and the stabilizers gelatin or sorbitol, may follow vac-cination. Anaphylactic reactions are rare, occurring in1/100 000 doses of vaccine administered.33

24 See No. 4, 2008, pp. 3744.25

See No. 32, 2009, pp. 325332.26 The heterogeneity I2value is dened as the proportion of the total variation in esti-

mated risk ratios due to between-trial heterogeneity rather than to chance.

27 See No. 14, 2004, pp. 129144.

28Grading of scientic evidence Table III (safety and immunogenicity in HIV-infectedchildren) with key references. Available from http://www.who.int/immunization/measles_grad_HIV.pdf

29 Demicheli V et al. Vaccines for measles, mumps and rubella in children. CochraneDatabase of Systematic Reviews, 2005 (4): CD004407.

30 Elliman D et al. Measles, mumps and rubella: prevention. In: Clinical Evidence. Lon-don, United Kingdom, BMJ Publishing, 2007 (http://clinicalevidence.bmj.com/ceweb/conditions/chd/0316/0316_I1.jsp).

31 Duclos P, Ward BJ. Measles vaccines: a review of adverse events. Drug Safety, 1998,19:435454.

32 Beeler J, Varricchio F, Wise R. Thrombocytopenia after immunization with measles

vaccines: review of the vaccine adverse events reporting system (1990 to 1994).Pediatric Infectious Disease Journal, 1996, 15:8890.

33 Salisbury DM, Campbell H, Edwards B. Measles rubella immunisation campaign inEngland one year on. London: Department of Health, 1995.

est recommande.24 En rgle gnrale, il convient dadministrer lesvaccins vivants soit simultanment, soit 4 semaines dintervalle. LeVPO est une exception cette rgle et on peut ladministrer nimportequel moment avant ou aprs la vaccination antirougeoleuse sans quil yait dinterfrences dans les rponses ces 2 vaccins.

VIH et vaccination contre la rougeoleLe Comit consultatif mondial de la scurit vaccinale (GACVS) a

rcemment demand un examen systmatique et une mta-analysede linnocuit et de limmunognicit du vaccin antirougeoleux chezlenfant infect par le VIH.25 Lanalyse na pas mis en vidence derisque accru dvnements indsirables graves chez les enfants sro-positifs pour le VIH par rapport aux autres. Le titrage des anticorpssriques aprs la vaccination a montr que la vaccination antirou-geoleuse lge de 6 mois permettait dobtenir un niveau de protec-tion identique chez lenfant infect par le VIH et celui qui navait past expos (risque relatif combin [RR] 1,05; intervalle de conance[IC] 95%, 0,831,34; htrognit I2, 65,7%; P=0.054 ).26 lge de9 mois, moins denfants infects par le VIH (avec ou sans signescliniques de sida) ont ragi au vaccin que denfants qui navaient past exposs au VIH (RR combin, 0,79; IC 95%, 0,611,02; htrog-nit I2, 81,5%; P=0.005). Deux tudes ont sembl indiquer que larponse des anticorps chez lenfant infect par le VIH disparaissait

plus vite que chez lenfant non infect. On a trs peu dinformationsconcernant les effets des traitements antirtroviraux hautement actifs(TAHA) sur la rponse la vaccination antirougeoleuse et des possi-bilits limites de comparer les enfants infects par le VIH vaccinset non vaccins. Il existe galement peu de donnes sur lefcacitclinique. Sur la base de cet examen, le Comit na pas trouv dl-ments justiant de modier les recommandations de lOMS de vacci-ner les enfants infects par le VIH et asymptomatiques.27, 28

Ractions indsirablesEn gnral les ractions indsirables suite la vaccination antirougeo-leuse sont bnignes et passagres.29, 30De lgres douleurs et une sensi-bilit au palper peuvent se produire au site dinjection dans les 24 heures;il sensuit parfois une lgre vre et une adnopathie locale. Environ

7 12 jours aprs la vaccination, jusqu 5% des sujets vaccins peuventprsenter une vre dau moins 39,4 C pendant 1 2 jours. Cette vreprovoque parfois des convulsions (chez environ 1/3 000 personnes). Unexanthme transitoire survient chez environ 2% des personnes et unpurpura thrombopnique chez 1/30 000 personnes vaccines.31, 32 lex-ception des ractions anaphylactiques, le risque dvnements indsira-bles est moindre aprs linjection de la seconde dose.

Aprs la vaccination, il arrive dobserver des ractions allergiques certains constituants du vaccin, dont la nomycine et les produitsstabilisants, glatine ou sorbitol. Les ractions anaphylactiques sontrares et surviennent pour 1/100 000 doses administres.33

24 Voir No4, 2008, pp. 37-44.25

Voir No

32, 2009, pp. 325-332.26 La valeur I2de lhtrognit se dnit comme la proportion de la variation totale des rapports

des risques estimatifs, imputables lhtrognit de 2 essais plutt quau hasard.

27 Voir No14, 2004, pp. 129-144.

28 Cotation des preuves scientiques Tableau III (innocuit et immunognicit chez lenfant in-fect par le VIH) avec rfrences cl. Disponible sur http://www.who.int/immunization/meas-les_grad_HIV.pdf

29 Demicheli V et al. Vaccines for measles, mumps and rubella in children. Cochrane Database ofSystematic Reviews, 2005 (4): CD004407.

30 Elliman D et al. Measles, mumps and rubella: prevention. In: Clinical Evidence. London, UnitedKingdom, BMJ Publishing, 2007 (http://clinicalevidence.bmj.com/ceweb/conditions/chd/0316/0316_I1.jsp).

31 Duclos P, Ward BJ. Measles vaccines: a review of adverse events. Drug Safety, 1998, 19:435454.

32 Beeler J, Varricchio F, Wise R. Thrombocytopenia after immunization with measles vaccines: re-

view of the vaccine adverse events reporting system (1990 to 1994). Pediatric Infectious DiseaseJournal, 1996, 15:8890.

33 Salisbury DM, Campbell H, Edwards B. Measles rubella immunisation campaign in England oneyear on. London: Department of Health, 1995.

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As with single measles vaccine, adverse events followingadministration of MMR and MMRV vaccines are mostlymild and transient, although the rate of febrile seizures oc-curring 710 days after the rst dose in children vaccinatedwith MMRV is about 2 times higher (9/10 000) than in chil-dren who receive MMR and varicella vaccines separately atthe same visit.34On rare occasions, symptoms characteris-tic of either rubella, mumps, or varicella may be observedfollowing administration of MCVs that include these vac-

cine viruses.

Extensive studies in different countries have demonstratedthat there is no increased risk of permanent neurologicalsequelae and no evidence to support an increased risk ofGuillain-Barr syndrome following administration of MCVs.Also, there is no scientic evidence to support reports thatmeasles vaccination may be a risk factor for inammatorybowel disease or for autism. The size of the studied popula-tions has afforded statistical power sufcient to detect evenrare associations.35

Indications, precautions and contraindicationsWhere no contraindications have been identied, measles vac-cine should be given to all infants and young children as partof national immunization programmes. The vaccine may alsobe offered to teenagers and adults likely to be susceptible andat risk of being exposed to measles virus for example, tothose who are travelling to areas where measles is endemic.The importance of vaccinating health workers is underlinedby the numerous measles outbreaks occurring in health insti-tutions, affecting both health workers and patients.

Administration of immunoglobulins or other antibody-con-taining blood products may neutralize the effect of the vac-cine for 311 months, depending on the dose of measlesantibody. Following measles vaccination, receipt of suchblood products should be avoided for 2 weeks if possible.

Mild, concurrent infections are not considered a contraindi-

cation to vaccination, but it should be avoided if the patienthas a high fever or other signs of serious disease. Theoreti-cally, measles vaccine alone or in combination with othervaccines should also be avoided by pregnant women. Beingin the early stages of HIV infection is not a contraindicationto measles immunization.

People with a history of an anaphylactic reaction to neomy-cin, gelatin or other components of the vaccine should notbe vaccinated. Furthermore, measles vaccine is contraindi-cated in people who are severely immunocompromised dueto congenital disease; severe HIV infection; advanced leukae-mia or lymphoma; serious malignant disease; treatment withhigh-dose steroids, alkylating agents or antimetabolites; orwho receive immunosuppressive therapeutic radiation.

Cost-effectiveness of measles vaccinationThe availability of an inexpensive and effective vaccinemakes measles immunization one of the most cost-effectivepublic health interventions across a range of developmentsettings. In Latin America, high coverage (95%) of both rou-tine immunization and campaign coverage was estimated toachieve considerable cost savings compared with moderatecoverage (85%) of routine immunization alone.36Vaccinationwith either 2 routine doses or 2 routine doses administered

34 What clinicians need to know about MMRV vaccine safety. Atlanta, US Centers forDisease Control and Prevention, April 2008 (http://www.cdc.gov/vaccinesafety/vsd/mmrv.htm).

35 Grading of scientic evidence Table IV (safety) with key references. Available fromhttp://www.who.int/immunization/measles_grad_safety.pdf

36 Acharya A et al. Cost-effectiveness of measles elimination in Latin America and theCaribbean: a prospective analysis. Vaccine, 2002, 20:33323341.

Comme pour le vaccin antirougeoleux isol, les manifestations post-vaccinales indsirables avec le ROR et le RORV sont la plupart dutemps bnignes et passagres, bien que la frquence des convulsionsfbriles 7 10 jours aprs ladministration de la premire dose deRORV chez lenfant soit environ 2 fois plus leve (9/10 000) que pourles enfants recevant sparment le ROR et le vaccin contre la varicellelors de la mme consultation.34 de rares occasions, on observe dessymptmes caractristiques de la rubole, des oreillons ou de la vari-celle aprs ladministration de vaccins antirougeoleux associant ces

autres virus.

Des tudes approfondies dans diffrents pays ont montr quil nyavait pas de risque accru de squelles neurologiques dnitives etque rien nindiquait une augmentation du risque de syndrome deGuillain-Barr aprs ladministration de vaccins antirougeoleux. Parailleurs, il nexiste aucune preuve scientique tayant les informa-tions selon lesquelles la vaccination antirougeoleuse pourrait tre unfacteur de risque de maladies inammatoires digestives ou dautisme.La taille des populations tudies permet dobtenir une puissancestatistique sufsante pour dtecter mme de rares associations.35

Indications, prcautions et contre-indicationsEn labsence de contre-indications, le vaccin antirougeoleux doit treadministr tous les nourrissons et les jeunes enfants dans le cadredes programmes de vaccination nationaux. On peut galement leproposer aux adolescents et aux adultes risquant dtre sensibles etde sexposer au virus par exemple ceux qui vont dans des zoneso la rougeole est endmique. La frquence des ambes de rougeolesurvenant dans les tablissements de sant et affectant le personnelcomme les patients souligne limportance de vacciner les personnelssoignants.

Ladministration dimmunoglobulines ou dautres produits sanguinscontenant des anticorps peut neutraliser leffet du vaccin pendant 3 11 mois, en fonction de la dose danticorps antirougeoleux. Aprsla vaccination, il faut viter si possible dadministrer ce type deproduits sanguins pendant 2 semaines.

Les infections bnignes concomitantes ne sont pas considres

comme une contre-indication la vaccination. En revanche, onvitera de vacciner si le patient prsente une forte vre ou dautressignes de maladie grave. En thorie, le vaccin antirougeoleux, seulou en association, ne doit pas tre administr la femme enceinte.Linfection VIH un stade prcoce nest pas non plus une contre-indication.

On vitera de vacciner les personnes ayant des antcdents de rac-tions anaphylactiques la nomycine, la glatine ou dautres consti-tuants du vaccin. En outre, le vaccin antirougeoleux est contre indi-qu dans les cas suivants: immunosuppression svre due unemaladie congnitale; infection VIH un stade avanc; leucmie oulymphome un stade avanc; maladies tumorales graves; traitementspar des strodes haute dose, des agents alkylants ou des antim-tabolites; patients traits par radiothrapie immunosuppressive.

Cot-efficacit de la vaccination antirougeoleuseLa disponibilit dun vaccin efcace et peu coteux fait de cette vacci-nation lune des interventions de sant publique les plus rentables dansde nombreuses situations des pays en dveloppement. En Amriquelatine, on a estim quune couverture leve (95%) de la vaccinationsystmatique comme des campagnes de vaccination, permettait defaire des conomiques consquentes, par rapport une couverture plusmodeste (85%) de la vaccination systmatique seulement.36Au Canadaet aux tats-Unis, on a estim que ladministration de 2 doses par la

34 What clinicians need to know about MMRV vaccine safety. Atlanta, US Centers for DiseaseControl and Prevention, April 2008 (http://www.cdc.gov/vaccinesafety/vsd/mmrv.htm).

35 Cotation des preuves scientiques Tableau IV (innocuit) avec rfrences cl. Disponible surhttp://www.who.int/immunization/measles_grad_safety.pdf

36 Acharya A et al. Cost-effectiveness of measles elimination in Latin America and the Caribbean:a prospective analysis. Vaccine, 2002, 20:33323341.

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with a catch-up campaign were both estimated to have anadvantageous costbenet ratio (>1) in Canada and theUnited States.37, 38 Where routine immunization coverage islow, measles vaccination through SIAs or mobile outreachservices has been shown to cost 9395% in all dis-tricts to prevent measles epidemics, reaching and maintain-ing high immunization coverage remains the cornerstone of

effective measles control. The coverage targets depend onnational goals for disease control. In countries aiming atreducing mortality from measles, immunization coverageshould be 90% at the national level and 80% in each dis -trict. Countries aiming at measles elimination should achieve95% coverage with both doses in every district.

At the 2005 World Health Assembly, all Member States en-dorsed the goal outlined in the Global Immunization Visionand Strategy framework of reducing by 90% global deathsfrom measles by 2010 compared with mortality in 2000.While there is no globally accepted goal for measles eradica-tion, 4 WHO regions (the Region of the Americas, the Euro-

37 Pelletier L et al. A benet-cost analysis of two-dose measles immunization in Ca -

nada. Vaccine, 1998, 16:989996.

38 Zhou F et al. An economic analysis of the current universal 2-dose measles-mumps-rubella vaccination program in the United States. International Journal of InfectiousDiseases, 2004, 189 Suppl 1:S131145.

39 Dayan GH et al. Cost-effectiveness of three different vaccination strategies againstmeasles in Zambian children. Vaccine, 2004, 22:475484.

40 Van Damme W, Van Lerberghe W. Strengthening health services to control epide-mics: empirical evidence from Guinea on its cost-effectiveness. Tropical Medicineand International Health, 2004, 9:281291.

41 Vijayaraghavan M et al. Economic evaluation of measles catch-up and follow-upcampaigns in Afghanistan in 2002 and 2003. Disasters, 2006, 30:256269.

42 Commission on Macroeconomics and Health. Macroeconomics and health: inves-ting in health for economic development. Report of the Commission on Macroeco-nomics and Health.Geneva, World Health Organization, 2001. (Also available fromhttp://whqlibdoc.who.int/publications/2001/924154550x.pdf).

43

Edejer TT et al. Cost effectiveness analysis of strategies for child health in deve-loping countries. British Medical Journal, 2005, 331:1177.

44 Fiedler JL, Chuko T. The cost of Child Health Days: a case study of Ethiopias Enhan-ced Outreach Strategy (EOS). Health Policy and Planning, 2008, 23:222233.

vaccination systmatique ou dans le cadre dune campagne de rattra-page avait dans les deux cas un rapport cot-avantage intressant(>1).37, 38 Quand la vaccination systmatique a une couverture faible,on a montr que la vaccination antirougeoleuse par des AVS ou desservices priphriques mobiles cotait

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pean Region, the Eastern Mediterranean Region and theWestern Pacic Region) have adopted measles elimination(that is, interruption of viral transmission within denedgeographical areas) as their regional goal. In the Region ofthe Americas, aggressive implementation of control strate-gies has already resulted in measles elimination. In the globalcontext, the priority is to improve measles control in theless-developed countries that account for a disproportionateamount of the global burden of measles.

Optimal age for MCV1In countries with ongoing transmission in which the risk ofmeasles mortality among infants remains high, MCV1 shouldbe administered at age 9 months. In these settings, on-timedelivery of MCV1 is important to ensure optimal protectionduring the susceptible period in infancy. Because many casesof measles occur in children aged >12 months who have notbeen vaccinated, routine delivery of MCV1 should not belimited to infants aged 912 months. All unvaccinated chil-dren aged 12 months should be offered MCV1 using everypossible opportunity when the child comes into contact withchildrens health services.

In countries with low rates of measles transmission (that is,those that are near elimination) and where there is thus alow risk of measles infection among infants, MCV1 may beadministered at age 12 months to take advantage of thehigher seroconversion rates achieved at this age. Increasingthe age of administration of MCV1 from 9 months to12 months represents a rational and desirable policy change.However, before implementing this change, policy-makersshould review local data on the age at which infants actuallyreceive measles vaccine, the coverage expected at 12 monthscompared with 9 months, and the age-specic measles inci-dence. Also, the immunogenicity and effectiveness of measlesvaccine administered at age 9 months compared with age12 months should be reviewed.

Interval between regular SIAsIn countries where health systems are moderately or weaklyfunctioning, regular measles SIAs are a highly effective strat-egy for protecting children who do not have access to routinehealth services. At the community level, SIAs rapidly increasepopulation immunity and thereby interrupt measles trans-mission (that is, achieve herd immunity). Because the riskof measles outbreaks is determined by the rate of accumula-tion of susceptible people in the population, programmesshould use data on vaccination coverage to monitor the ac-cumulation of susceptible people and conduct follow-up SIAsbefore the number of susceptible children of pre-school agereaches the size of a birth cohort. This approach has beenfound to be programmatically useful and sufciently accu-rate to prevent large outbreaks.

Introduction of routine MCV2

MCV2 may be added to the routine immunization schedulein countries that have achieved 80% coverage of MCV1 atthe national level for 3 consecutive years as determined bythe most accurate means available (for example, a well con-ducted population-based survey or WHO/UNICEF estimates).In general, countries that do not meet this criterion shouldprioritize improving MCV1 coverage and conducting high-quality follow-up SIAs, rather than adding MCV2 to theirroutine schedule.

Since the addition of routine MCV2 covers only a single birthcohort and it takes time to achieve high coverage, countriesshould not interrupt regular SIAs. The accumulation of sus-ceptible people should continue to be monitored subsequentto the introduction of routine administration of MCV2, and

Mditerrane orientale et Pacique occidental) ont adopt au niveaurgional un but dlimination (cest--dire linterruption de la trans-mission virale dans des zones gographiques bien dnies). Dans laRgion des Amriques, lapplication nergique de stratgies de luttea dj permis dobtenir llimination. lchelle mondiale, la prioritconsiste amliorer la lutte dans les pays moins dvelopps quisupportent une part disproportionne du fardeau de la rougeole.

ge optimal pour la premire dose de vaccin antirougeoleuxDans les pays ayant une transmission continue avec persistance dunrisque lev de mortalit par rougeole pour les nourrissons, la premiredose doit tre administre lge de 9 mois. Dans ces conditions, il estimportant de ladministrer temps pour garantir une protection opti-male pendant la priode de sensibilit des nourrissons. Comme denombreux cas de rougeole surviennent chez les enfants gs de >12 moiset qui nont pas t vaccins, ladministration systmatique de la premiredose ne doit pas se limiter aux enfants entre 9 et 12 mois. partir delge de 12 mois, on saisira toutes les occasions possibles pour proposercette vaccination tout enfant non vaccin, par exemple quand il estamen en consultation dans les services de sant pdiatrique.

Dans les pays ayant de faibles niveaux de transmission de la rougeole(cest--dire ceux qui sapprochent de llimination) et o le risquede rougeole est donc faible pour les nourrissons, on peut administrerla premire dose du vaccin antirougeoleux lge de 12 mois pourtirer parti des taux plus levs de sroconversion que lon obtient cet ge. Le fait de reporter cette vaccination lge de 12 mois consti-tue une modication rationnelle et souhaitable de la politique. Toute-fois, avant dinstaurer ce changement, les responsables politiquesdoivent passer en revue les donnes locales sur lge auquel les nour-rissons sont rellement vaccins contre la rougeole, sur la couvertureescompte 12 mois par rapport celle pour les enfants de 9 mois,ainsi que sur lincidence de la maladie en fonction de lge. Il convientaussi dexaminer et de comparer limmunognicit et lefcacit duvaccin administr 9 mois et 12 mois.

Intervalle entre les AVS rguliresDans les pays o les systmes de sant fonctionnent moyennementou pas assez bien, les AVS rgulires contre la rougeole constituentune stratgie trs efcace pour protger les enfants qui nont pasaccs aux services de sant ordinaires. Au niveau communautaire, lesAVS augmentent rapidement limmunit de la population et inter-rompent ainsi la transmission de la rougeole (immunit collective).Comme le risque de ambe est dtermin par laccumulation depersonnes sensibles dans une population, les programmes devraientse servir des donnes sur la couverture vaccinale pour contrlerlaugmentation du nombre de sujets sensibles et organiser des AVSde suivi avant que le nombre denfants sensibles dge prscolaire necorresponde aux effectifs dune cohorte de naissance. Cette approchesest rvle utile pour les programmes et sufsamment prcise pourviter de grandes ambes.

Introduction de ladministration systmatique de la secondedose de vaccin antirougeoleuxElle peut tre ajout au calendrier des vaccinations systmatiquesdans les pays ayant atteint une couverture de la premire dose daumoins 80% pendant 3 annes conscutives, daprs les moyens statis-tiques disponibles les plus prcis possible (par exemple une enquteen population bien mene ou les estimations OMS/UNICEF). En gn-ral, les pays qui ne remplissent pas ce critre doivent en prioritamliorer la couverture de la premire dose et organiser des AVS desuivi de qualit, plutt que dajouter la seconde dose leur calendrierdes vaccinations systmatiques.

Comme lajout dune seconde dose systmatique ne couvre au dpart quuneseule cohorte de naissance, il faut du temps pour atteindre une couvertureleve et les pays ne devraient pas interrompre les AVS rgulires. On conti-nuera alors de surveiller laugmentation du nombre des sujets sensiblesaprs lintroduction de ladministration systmatique de la seconde dose et

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an SIA should be conducted before the number susceptiblechildren of pre-school age reaches the size of a birth cohort.

Experience in the Region of the Americas has shown thatmeasles elimination can be achieved through high coverageof MCV1 and the use of regular, high-quality SIAs. Hence,adding routine administration of MCV2 is not necessary tointerrupt measles transmission. Nevertheless, a country maydecide to add MCV2 to their routine schedule (while continu-

ing SIAs) for one or more of the following reasons: (i) toslow the accumulation of susceptible children and therebyallow a lengthening of the interval between SIAs; (ii) to de-crease the countrys reliance on SIAs and eventually stopSIAs once high population immunity (>93%) can be main-tained with a routine 2-dose schedule alone; and (iii) to es-tablish a well-child visit during the second year of life tomaximize linkages with other routine doses (for example,the diphtheriatetanuspertussis vaccine [DTP] booster) aswell as with other health interventions such as deworming,delivering mosquito nets or administering vitamin A.

Before introducing routine delivery of MCV2, countriesshould determine a suitable age for administering this dose,establish a system for recording doses both for the indi-vidual (for example, with an immunization card) and thehealth system (for example, with a vaccination register), andtrain health staff to ensure the timely scheduling of dosesand tracking of those who are missed.

Optimal timing of routine delivery of MCV2

Countries with ongoing measles transmission and MCV1delivered at age 9 months, should administer the routinedose of MCV2 at age 1518 months. The minimum intervalbetween MCV1 and MCV2 is 1 month. Providing routineMCV2 to children in their second year of life reduces therate of accumulation of susceptible children and the risk of

an outbreak.In countries with low measles transmission (that is, thosethat are near elimination) and where MCV1 is administeredat age 12 months, the optimal age for delivering routineMCV2 is based on programmatic considerations that achievethe highest coverage of MCV2 and, hence, the highest popu-lation immunity. Administration of MCV2 at age 1518months ensures early protection of the individual, slows ac-cumulation of susceptible young children and may corre-spond with other routine immunizations (for example, a DTPbooster). If MCV1 coverage is high (>90%) and school enrol-ment is high (>95%), administration of routine MCV2 atschool entry may prove an effective strategy for achievinghigh coverage and preventing outbreaks in schools.

Criteria for stopping follow-up SIAsFor countries that have relied on regular SIAs to achievehigh population immunity, cessation of SIAs should be con-sidered only when >9095% immunization coverage hasbeen achieved at the national level for both MCV1 and rou-tine MCV2 as determined by the most accurate means avail-able for a period of at least 3 consecutive years.

Before stopping SIAs, a review should be conducted by anational committee (such as the national immunization ad-visory group). The committee should examine the following:historical data on immunization coverage for MCV1, routine

MCV2 and SIAs both at the national and the district45 level,

une AVS sera organise avant que le nombre denfants sensibles dge pr-scolaire ne corresponde aux effectifs dune cohorte de naissance.

Lexprience dans la Rgion des Amriques a montr quon pouvait arri-ver liminer la rougeole en instituant une couverture leve de lapremire dose du vaccin antirougeoleux et en faisant appel des AVSrgulires de qualit. Par consquent, il nest pas ncessaire dajouter lad-ministration systmatique dune seconde dose pour interrompre la trans-mission. Nanmoins, un pays peut dcider dajouter une seconde dose de

vaccin antirougeoleux au calendrier des vaccinations systmatiques (touten poursuivant les AVS) pour une ou plusieurs des raisons suivantes:i) ralentir laugmentation du nombre des enfants sensibles et ainsi dimi-nuer la frquence des AVS, ii) organiser progressivement moins dAVS etnir par les interrompre ds quil est possible de maintenir une immunitleve dans la population (>93%) par la seule application dun calendriersystmatique de 2 doses, iii) instaurer une consultation de contrle pendantla deuxime anne de vie de lenfant pour tirer le meilleur parti des liensavec dautres vaccinations systmatiques (par exemple le rappel du vaccinanti-diphtrie-ttanos-coqueluche [DTC]), ainsi que dautres interventionssanitaires, comme ladministration de vermifuges, la distribution de mous-tiquaires ou ladministration de vitamine A.

Avant dajouter la seconde dose du vaccin antirougeoleux leur calen-drier des vaccinations systmatiques, les pays doivent dterminer lgeauquel il convient dadministrer cette dose, instaurer un systme den-registrement des doses administres, la fois pour le sujet vaccin(carte de vaccination, par exemple) et pour le systme de sant (regis-tre des vaccinations, par exemple) et former le personnel de sant pourque ladministration des doses soit programme en temps opportunet que le suivi des enfants qui nont pas t vaccins soit assur.

Moment optimal de ladministration systmatiquede la seconde dose du vaccin antirougeoleuxLes pays o la transmission de la rougeole est continuelle et o lapremire dose est administre lge de 9 mois devraient prvoir lad-ministration systmatique de la seconde dose un ge compris entre15 et 18 mois. Lintervalle minimum entre les 2 doses est de 1 mois.Ladministration systmatique de la seconde dose aux enfants dans leurdeuxime anne de vie diminue la vitesse laquelle le nombre desenfants sensibles augmente et le risque de ambes de rougeole.

Dans les pays o la transmission de la rougeole est faible (cest--direceux qui sapprochent de llimination) et qui administrent lapremire dose lge de 12 mois, lge optimal pour ladministrationsystmatique de la seconde dose dpend des considrations program-matiques qui permettront datteindre la meilleure couverture et,donc, limmunit la plus leve dans la population. Ladministrationde la seconde dose un ge compris entre 15 et 18 mois confre uneprotection prcoce au sujet vaccin, ralentit laccumulation denfantssensibles en bas ge et peut avoir lieu loccasion dautres vaccina-tions systmatiques (par exemple le rappel du DTC). Dans les paysayant une couverture leve de la premire dose du vaccin antirou-geoleux (>90%) et un fort taux de scolarisation (>95%), ladminis-tration systmatique de la seconde dose au moment de lentre

lcole peut savrer une stratgie efcace pour atteindre une couver-ture leve et viter les ambes en milieu scolaire.

Critres pour mettre fin aux AVSLes pays qui ont recours des AVS rgulires pour parvenir untaux dimmunit lev dans la population, nenvisageront pas demettre n ces AVS avant que ladministration systmatique des2 doses de vaccin antirougeoleux natteigne une couverture daumoins 90 95% au niveau national, daprs les statistiques les plusexactes possibles pendant au moins trois annes conscutives.

Avant de mettre n aux AVS, un comit national (groupe consultatifnational pour la vaccination, par exemple) doit examiner la situation.Il doit tudier les points suivants: les donnes historiques sur lacouverture de la premire et de la deuxime dose systmatiques, ainsi

que des AVS, au niveau national et celui des districts,45 le degr

45 A district is dened as the third administrative level in a country. 45 Le district est dni comme le troisime niveau dadministration dans un pays.

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