Académique Documents
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349
This is the first WHO position paper on a dengue Le prsent document est la premire note de synthse de lOMS
vaccine. It focuses primarily on the available evidence traitant de la vaccination contre la dengue. Il contient essen-
concerning the only dengue vaccine to have been regis- tiellement les informations disponibles sur le seul vaccin contre
tered by National Regulatory Authorities (NRA). Recom- la dengue qui est ce jour homologu par les autorits natio-
mendations on the use of this dengue vaccine were nales de rglementation. Les recommandations relatives luti-
discussed by SAGE in April 2016; evidence presented at lisation de ce vaccin contre la dengue ont t examines par le
that SAGE meeting can be accessed at: http://www.who. SAGE en avril 2016; les lments prsents lors de cette runion
int/immunization/sage/previous/en/index.html. peuvent tre consults ladresse: http://www.who.int/immuni-
zation/sage/previous/en/index.html.
Background Gnralits
Epidemiology pidmiologie
The number of dengue cases reported annually to WHO Le nombre de cas de dengue notifis chaque anne lOMS a
has increased from 0.4 to 1.3 million in the decade augment, passant de 0,4 million 1,3 million dans la priode
19962005, reaching 2.2 million in 2010 and 3.2 million 1996-2005 pour atteindre 2,2 millions en 2010 et 3,2 millions en
in 2015.2, 3 There is substantial under-reporting of 2015.2, 3 On observe une forte sous-notification des cas de
dengue within health systems and to WHO.4 Based on dengue, tant au sein des systmes de sant qu lOMS.4 Linci-
mathematical modelling, the global annual incidence dence annuelle mondiale de la dengue, estime par modlisa-
has been estimated at about 50 million 100 million tion mathmatique, tait de quelque 50-100 millions de cas
symptomatic cases in recent years, predominantly in symptomatiques au cours des dernires annes, les rgions les
Asia, followed by Latin America and Africa, with clinical plus touches tant essentiellement lAsie, suivie de lAmrique
cases likely to represent about 25% of all dengue virus latine et de lAfrique. noter que les cas cliniques reprsentent
infections.5, 6 In 2013 dengue was estimated to be respon- probablement environ 25% de toutes les infections par le virus
sible for approximately 3.2 million severe cases and 9000 de la dengue.5, 6 On estime quen 2013, la dengue tait respon-
deaths, the majority occurring in lower middle income sable denviron 3,2 millions de cas de maladie svre et
countries, and for 1.1 million disability adjusted life 9000 dcs, principalement dans les pays revenu intermdiaire
years (DALYs) globally.5 de la tranche infrieure, ainsi que de 1,1 million dannes de
vie ajustes sur lincapacit (DALY) lchelle mondiale.5
Dengue viruses are primarily maintained in a human- Les virus de la dengue se transmettent essentiellement selon
to-mosquito-to-human cycle. The primary vector is the un cycle homme-moustique-homme. Le vecteur principal de la
Aedes aegypti mosquito, which is highly adapted to maladie est le moustique Aedes aegypti, qui est particulire-
human habitations. Aedes albopictus can also sustain ment bien adapt lhabitat humain. Aedes albopictus peut
dengue virus transmission in humans. Other species galement transmettre le virus de la dengue lhomme. Dautres
maintain a monkey-mosquito cycle in south-east Asia espces prsentent un cycle de transmission singe-moustique
and western Africa. Dengue virus transmission from en Asie du Sud-Est et en Afrique occidentale. La transmission
non-human primates to humans appears to be rare. The de la dengue des primates non-humains lhomme semble rare.
spread of vectors following urbanization and the decline La propagation des vecteurs, rsultant de lurbanisation et du
in vector-control efforts has partially contributed to the dclin des efforts de lutte antivectorielle, a contribu en partie
increased incidence of dengue virus infections. However, laugmentation de lincidence des infections par les virus de
dengue is not confined to urban settings and is increas- la dengue. Toutefois, la dengue ne se limite pas aux zones
ingly reported from rural areas. Additionally, factors urbaines, des cas de plus en plus nombreux tant signals en
such as population growth, globalization and travel, and milieu rural. En outre, certains facteurs comme la croissance
climate change facilitate increased transmission of dmographique, la mondialisation, lintensification des voyages
dengue viruses. Dengue exhibits substantial temporal et le changement climatique favorisent une transmission accrue
and geographic variability.7 des virus de la dengue. La maladie prsente une grande varia-
bilit dans le temps et dans lespace.7
Transmission intensity as well as population structure Lintensit de la transmission, ainsi que la structure dmogra-
and demographic factors can affect the age distribution phique et dautres facteurs lis la population, peuvent influer
2
Global Strategy for dengue prevention and control, 20122020. World Health Orga- 2
Global Strategy for dengue prevention and control, 20122020. World Health Organization,
nization, Geneva, Switzerland, 2012. Available at http://apps.who.int/iris/bitstre Geneva, Switzerland, 2012. Disponible ladresse: http://apps.who.int/iris/bitstre
am/10665/75303/1/9789241504034_eng.pdf am/10665/75303/1/9789241504034_eng.pdf
3
Dengue and severe dengue (Fact sheet N117). World Health Organization, Geneva, 3
Dengue et dengue svre (Aide-mmoire N 117). Organisation mondiale de la Sant, Genve
Switzerland, 2016 [cited 24 June 2016]. Available from: http://www.who.int/me- (Suisse), 2016 [cit le 24 juin 2016]. Disponible ladresse: http://www.who.int/mediacentre/
diacentre/factsheets/fs117/en/ factsheets/fs117/fr/
4
Beatty ME, et al. Health economics of dengue: a systematic literature review and 4
Beatty ME, et al. Health economics of dengue: a systematic literature review and expert panels
expert panels assessment. Am J Trop Med Hyg. 2011;84(3):473488. assessment. Am J Trop Med Hyg. 2011;84(3):473488.
5
Stanaway JD, et al. The global burden of dengue: an analysis from the Global Bur- 5
Stanaway JD, et al. The global burden of dengue: an analysis from the Global Burden of Disease
den of Disease Study 2013. Lancet Infect Dis. 2016 Jun; 16(6): 712723. Study 2013. Lancet Infect Dis. 2016 Jun; 16(6): 712723.
6
Bhatt S, et al. The global distribution and burden of dengue. Nature. 6
Bhatt S, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504507.
2013;496(7446):504507.
7
Limkittikul K, et al. Epidemiological trends of dengue disease in Thailand (2000 7
Limkittikul K, et al. Epidemiological trends of dengue disease in Thailand (20002011): a syste-
2011): a systematic literature review. PLoS Negl Trop Dis. 2014;8(11):e3241. matic literature review. PLoS Negl Trop Dis. 2014;8(11):e3241.
Disease Maladie
The majority of dengue virus infections are asymptom- La plupart des infections par le virus de la dengue sont asymp-
atic. For clinical cases the incubation period is usually tomatiques. Dans les cas cliniques, la priode dincubation dure
47 days but can be in the range 314 days. The most gnralement 4 7 jours, mais la plage possible est de 3
common presentation is the sudden onset of fever 14 jours. Le tableau clinique se caractrise le plus souvent par
accompanied by headache, retro-orbital pain, general- une fivre soudaine, accompagne de cphales, de douleurs
ized myalgia and arthralgia, flushing of the face, rtro-orbitaires, de myalgie et darthralgie gnralises, de bouf-
anorexia, abdominal pain and nausea. Rash is frequently fes congestives du visage, danorexie, de douleurs abdominales
seen on the trunk, on the medial aspect of the arms et de nauses. On observe frquemment une ruption cutane
and thighs, and on plantar and palmar surfaces and can sur le tronc, la face mdiale des bras et des cuisses, et les
be macular, maculopapular, morbilliform, scarlatini- surfaces plantaires et palmaires; cette ruption peut tre macu-
form or petechial. Laboratory-detected abnormalities laire, maculopapulaire, morbilliforme, scarlatiniforme ou pt-
may include leukopenia and thrombocytopenia. Indi- chiale. Les analyses de laboratoire peuvent rvler des anoma-
viduals infected multiple times with different dengue lies, notamment une leucopnie et une thrombopnie. Les
virus serotypes may experience multiple clinical personnes infectes multiples reprises avec diffrents sro-
episodes. There is no chronic infection with dengue types du virus de la dengue peuvent connatre plusieurs
virus or carriage state known. pisodes cliniques. Aucun tat de portage ou dinfection chro-
nique par le virus de la dengue nest connu ce jour.
For the purpose of clinical management, WHO classifies Aux fins de la prise en charge clinique, lOMS a tabli les cat-
dengue illness as (i) dengue with or without warning gories suivantes: i) dengue avec ou sans signes annonciateurs
signs for progression towards severe dengue and dune progression de la maladie vers une dengue svre et
Restrepo AC, et al. National spatial and temporal patterns of notified dengue cases,
8 8
Restrepo AC, et al. National spatial and temporal patterns of notified dengue cases, Colombia
Colombia 20072010. Trop Med Int Health. 2014;19(7):863871. 20072010. Trop Med Int Health. 2014;19(7):863871.
9
Messina JP, et al. Global spread of dengue virus types: mapping the 70 year history. 9
Messina JP, et al. Global spread of dengue virus types: mapping the 70 year history. Trends Mi-
Trends Microbiol. 2014;22(3):138146. crobiol. 2014;22(3):138146.
10
Guzman MG, et al. Dengue. Lancet. 2015;385(9966):453465. 10
Guzman MG, et al. Dengue. Lancet. 2015;385(9966):453465.
11
World Health Organization. Dengue Guidelines for Diagnosis, Treatment, Preven- 11
World Health Organization. Dengue Guidelines for Diagnosis, Treatment, Prevention and
tion and Control. Geneva, Switzerland: 2009. Available at http://www.who.int/tdr/ Control. Geneva, Switzerland: 2009. Disponible ladresse: http://www.who.int/tdr/publica-
publications/documents/dengue-diagnosis.pdf tions/documents/dengue-diagnosis.pdf.
12
Hunsperger EA, et al. The Performance of Dengue Diagnostic Tests in a Single-Spe- 12
Hunsperger EA, et al. The Performance of Dengue Diagnostic Tests in a Single-Specimen Dia-
cimen Diagnostic Algorithm. J Infect Dis. 2016. gnostic Algorithm. J Infect Dis. 2016.
13
Monath TP. Dengue: the risk to developed and developing countries. Proc Natl Acad 13
Monath TP. Dengue: the risk to developed and developing countries. Proc Natl Acad Sci U S A.
Sci U S A. 1994;91(7):23952400. 1994;91(7):23952400.
14
Simmons CP, et al. Recent advances in dengue pathogenesis and clinical manage- 14
Simmons CP, et al. Recent advances in dengue pathogenesis and clinical management. Vaccine.
ment. Vaccine. 2015;33(50):70617068. 2015;33(50):70617068.
15
Achee NL, et al. A critical assessment of vector control for dengue prevention. PLoS 15
Achee NL, et al. A critical assessment of vector control for dengue prevention. PLoS Negl Trop
Negl Trop Dis. 2015;9(5):e0003655. Dis. 2015;9(5):e0003655.
352 WEEKLY EPIDEMIOLOGICAL RECORD, NO 30, 29 JULY 2016
Some common strategies aim to prevent mosquitoes Certaines stratgies couramment employes visent empcher les
from accessing egg-laying habitats, using environmental moustiques daccder aux gtes de ponte grce des interventions
management interventions including: disposing of solid de gestion de lenvironnement, consistant notamment liminer
waste properly; removing artificial man-made mosquito correctement les dchets solides; liminer les habitats de mous-
habitats; covering, emptying and cleaning of domestic tiques dorigine humaine artificielle; couvrir, vider et nettoyer
water storage containers on a weekly basis; applying toutes les semaines les conteneurs servant au stockage de leau
appropriate insecticides or predators to outdoor water domestique; pandre des insecticides ou utiliser des prdateurs
storage containers; using personal and household adapts pour leau stocke lextrieur; prendre des mesures de
protection such as window screens, long-sleeved clothes, protection individuelle et de protection du foyer par la pose
insecticide or repellent treated materials, coils and de moustiquaires aux fentres, le port de vtements manches
vaporizers; improving community participation and longues et lutilisation de matriels imprgns dinsecticide, de
mobilization for sustained vector control; and applying spirales et de pulvrisateurs; amliorer la participation et la
insecticides using space sprays during outbreaks as one mobilisation des communauts pour une lutte antivectorielle
of the emergency vector control measures. durable; et procder des pulvrisations dinsecticides titre de
mesure antivectorielle durgence en situation de flambe.
16
Rodrigo WW, et al. Dengue virus neutralization is modulated by IgG antibody sub- 16
Rodrigo WW, et al. Dengue virus neutralization is modulated by IgG antibody subclass and Fc-
class and Fcgamma receptor subtype. Virology. 2009;394(2):175182. gamma receptor subtype. Virology. 2009;394(2):175182.
17
Wu RS, et al. Neutralization of dengue virus in the presence of Fc receptor-mediated 17
Wu RS, et al. Neutralization of dengue virus in the presence of Fc receptor-mediated phagocy-
phagocytosis distinguishes serotype-specific from cross-neutralizing antibodies. tosis distinguishes serotype-specific from cross-neutralizing antibodies. Antiviral Res.
Antiviral Res. 2012;96(3):340343. 2012;96(3):340343.
18
Montoya M, et al. Symptomatic versus inapparent outcome in repeat dengue virus 18
Montoya M, et al. Symptomatic versus inapparent outcome in repeat dengue virus infections is
infections is influenced by the time interval between infections and study year. PLoS influenced by the time interval between infections and study year. PLoS Negl Trop Dis.
Negl Trop Dis. 2013;7(8):e2357. 2013;7(8):e2357.
19
Reich NG, et al. Interactions between serotypes of dengue highlight epidemiologi- 19
Reich NG, et al. Interactions between serotypes of dengue highlight epidemiological impact of
cal impact of cross-immunity. J R Soc Interface. 2013;10(86):20130414. cross-immunity. J R Soc Interface. 2013;10(86):20130414.
20
Endy TP, et al. Prospective cohort studies of dengue viral transmission and severity 20
Endy TP, et al. Prospective cohort studies of dengue viral transmission and severity of disease.
of disease. Curr Top Microbiol Immunol. 2010;338:113. Curr Top Microbiol Immunol. 2010;338:113.
21
Graham RR, et al. A prospective seroepidemiologic study on dengue in children four 21
Graham RR, et al. A prospective seroepidemiologic study on dengue in children four to nine
to nine years of age in Yogyakarta, Indonesia I. studies in 19951996. Am J Trop years of age in Yogyakarta, Indonesia I. studies in 19951996. Am J Trop Med Hyg.
Med Hyg. 1999;61(3):412419. 1999;61(3):412419.
22
Thein S, et al. Risk factors in dengue shock syndrome. Ibid. 1997;56(5):566572. 22
Thein S, et al. Risk factors in dengue shock syndrome. Ibid. 1997;56(5):566572.
23
Balmaseda A, et al. High seroprevalence of antibodies against dengue virus in a 23
Balmaseda A, et al. High seroprevalence of antibodies against dengue virus in a prospective
prospective study of schoolchildren in Managua, Nicaragua. Trop Med Int Health. study of schoolchildren in Managua, Nicaragua. Trop Med Int Health. 2006;11(6):935942.
2006;11(6):935942.
24
Olkowski S, et al. Reduced risk of disease during postsecondary dengue virus infec- 24
Olkowski S, et al. Reduced risk of disease during postsecondary dengue virus infections. J Infect
tions. J Infect Dis. 2013;208(6):10261033. Dis. 2013;208(6):10261033.
Phase III Trial to Evaluate Efficacy and Safety of a Dengue 1,2,3,4 (Attenuated)
25
Phase III Trial to Evaluate Efficacy and Safety of a Dengue 1,2,3,4 (Attenuated) Vaccine (https://
25
Immunogenicity Immunognicit
There is as yet no generally accepted correlate of protec- ce jour, il nexiste pas dindicateur gnralement reconnu de
tion induced by CYD-TDV, although a relationship has la protection confre par le CYD-TDV, bien quune relation ait
been described between vaccine-induced neutralizing t dcrite entre les titres danticorps neutralisants induits par
antibody titres and probability of virologically- la vaccination et la probabilit de survenue dune dengue viro-
confirmed dengue illness.31 logiquement confirme.31
CYD-TDV induces neutralizing antibodies against all 4 Le CYD-TDV induit la production danticorps neutralisants
dengue virus serotypes, as measured by PRNT50. Post- dirigs contre lensemble des 4 srotypes du virus de la dengue,
vaccination titres are higher in individuals who were comme indiqu par la mesure de PRNT50. Les titres aprs vacci-
30
WHO Policy Statement: Multi-dose Vial Policy (MDVP). World Health Organization, Dclaration de politique gnrale de lOMS: rvision de la politique relative aux flacons multi-
30
Geneva, Switzerland, 2014. Available at http://apps.who.int/iris/ doses. Organisation mondiale de la Sant, Genve (Suisse), 2014. Disponible ladresse: http://
bitstream/10665/135972/1/WHO_IVB_14.07_eng.pdf apps.who.int/iris/bitstream/10665/135973/1/WHO_IVB_14.07F_fre.pdf
Jackson N, et al. Abstract 576: Investigations of the observed efficacy of the CYD
31
Jackson N, et al. Abstract 576: Investigations of the observed efficacy of the CYD tetravalent
31
tetravalent dengue vaccine in the Phase 2b trial in Ratchaburi, Thailand. The Ame- dengue vaccine in the Phase 2b trial in Ratchaburi, Thailand. The American Journal of Tropical
rican Journal of Tropical Medicine and Hygiene. 2014;91(5 Suppl 1):172. Medicine and Hygiene. 2014;91(5 Suppl 1):172.
Efficacy Efficacit
Vaccine efficacy against virologically-confirmed dengue Lefficacit du vaccin contre la dengue virologiquement confir-
illness was assessed during the active phase of surveil- me a t value durant la phase active de surveillance des
lance (25 months post-enrolment) in CYD14 and CYD15. essais CYD14 et CYD15 (priode de 25 mois aprs linclusion
Per protocol vaccine efficacy against virologically- dans ltude). Lanalyse selon le protocole a montr que leffi-
confirmed symptomatic dengue illness of any serotype cacit du vaccin contre la dengue symptomatique virologique-
was 56.5% (95% CI 43.8%66.4%) in CYD14,28 and 60.8% ment confirme, tous srotypes confondus, tait de 56,5% (IC
(95% CI 52.0%68.0%) in CYD1529 (from one month post 95%: 43,8%-66,4%) dans lessai CYD1428 et de 60,8% (IC 95%:
dose 3 for 12 months). In both trials, vaccine efficacy 52,0%-68,0%) dans lessai CYD1529 (priode de 12 mois comp-
was lower against serotypes 1 (50.2%, 95% CI 35.6% ter du mois suivant la dose 3). Dans les 2 essais, le vaccin tait
61.5%) and 2 (39.6%, 95% CI 18.7%55.2%) than against moins efficace contre les srotypes 1 (50,2%, IC 95%: 35,6%-
serotypes 3 (74.9%, 95% CI 65.1%82.0%) and 4 (76.6%, 61,5%) et 2 (39,6%, IC 95%: 18,7%-55,2%) que contre les sro-
95% CI 65.0%84.4%). Vaccine efficacy estimates were types 3 (74,9%, IC 95%: 65,1%-82,0%) et 4 (76,6%, IC 95%:
similar in the 2 Phase 3 trials despite variable epide- 65,0%-84,4%). Les estimations de lefficacit vaccinale taient
miological settings and ages at vaccination (214 years comparables dans ces 2 essais de phase 3, malgr les diffrences
in CYD14 and 916 years in CYD15).34 de contexte pidmiologique et dge la vaccination (2-14 ans
pour CYD14 et 9-16 ans pour CYD15).34
32
Background Paper on Dengue Vaccines. World Health Organization, Geneva, Swit- 32
Background Paper on Dengue Vaccines. World Health Organization, Geneva, Switzerland, 2016.
zerland, 2016. Available at http://www.who.int/entity/immunization/sage/mee- Disponible ladresse: http://www.who.int/entity/immunization/sage/meetings/2016/april/1_
tings/2016/april/1_Background_Paper_Dengue_Vaccines_2016_03_17.pdf Background_Paper_Dengue_Vaccines_2016_03_17.pdf
33
No clinical data have been generated from individuals older than 45 years living in 33
Aucune donne clinique na t produite concernant les sujets de plus de 45 ans vivant dans
endemic settings. des zones dendmie.
34
GRADE Table 1. See footnote 32. 34
Tableau GRADE 1. Voir note de bas de page 32.
Hadinegoro SR, et al. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions
35
Hadinegoro SR, et al. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic
35
36
N. Ferguson Comparative modelling of dengue vaccine impact. Meeting of the Stra- 36
N. Ferguson Comparative modelling of dengue vaccine impact. Meeting of the Strategic Advi-
tegic Advisory Group of Experts (SAGE) on Immunization, 2016. Geneva, Switzer- sory Group of Experts (SAGE) on Immunization, 2016. Geneva, Switzerland. Voir diapositive 7,
land. See slide 7, available at http://www.who.int/immunization/sage/ disponible ladresse: http://www.who.int/immunization/sage/meetings/2016/april/3_Fergu-
meetings/2016/april/3_Ferguson_Comparative_Dengue_Modelling_SAGE. son_Comparative_Dengue_Modelling_SAGE.pdf?ua=1
pdf?ua=1
37
GRADE Table 2. See footnote 32. 37
Tableau GRADE 2. Voir note de bas de page 32.
38
Chuenkitmongkol S, et al. Safety of a recombinant live attenuated tetravalent 38
Chuenkitmongkol S, et al. Safety of a recombinant live attenuated tetravalent dengue vaccine:
dengue vaccine: pooled analysis of 20,667 individuals aged 9 through 60 years of pooled analysis of 20,667 individuals aged 9 through 60 years of age. Joint International Tropi-
age. Joint International Tropical Medicine Meeting; 2015; Bangkok, Thailand. cal Medicine Meeting; 2015; Bangkok, Thailand.
39
GRADE Table 3. See footnote 32. 39
Tableau GRADE 3. Voir note de bas de page 32.
40
Flasche S et al., Comparative modelling of dengue vaccine public health impact. 40
Flasche S et al., Comparative modelling of dengue vaccine public health impact. Disponible
Available at http://www.who.int/immunization/sage/meetings/2016/april/2_CMD- ladresse: http://www.who.int/immunization/sage/meetings/2016/april/2_CMDVI_Report_FI-
VI_Report_FINAL.pdf. [A manuscript is in preparation that will provide updated NAL.pdf. [Un document contenant des figures actualises est en cours de prparation].
figures].
RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 30, 29 JUILLET 2016 359
fective or may theoretically even increase the future risk lge partir duquel le vaccin est indiqu. Il est possible que
of hospitalized or severe dengue illness in those who la vaccination soit inefficace, ou mme, en thorie, quelle
are seronegative at the time of first vaccination regard- augmente le risque futur dhospitalisation ou de dengue svre
less of age.41 If this is the case, even in high transmission chez les personnes srongatives au moment de la premire
settings there may be increased risk among seronega- vaccination, quel que soit leur ge.41 Si cest le cas, il pourrait
tive persons despite a reduction in dengue illness at the y avoir, mme dans des contextes de forte transmission, un
population level. Although data are limited by the trial risque accru pour les personnes srongatives, en dpit dun
designs, data collected from the immunogenicity subset recul de la dengue au niveau de la population. Bien que les
and followed over the 5 years of the ongoing Phase 3 donnes soient limites par les protocoles dessai, les donnes
and Phase 2b trials did not show evidence of enhanced provenant de la sous-population dtude de limmunognicit,
risk in seronegative individuals 9 years of age, whereas suivie durant les 5 annes de la phase 2b et de la phase 3
there was a suggestion of enhanced risk in seronegative actuelle, ne rvlent pas de risque accru pour les personnes
children <9 years of age.32, 42 srongatives de 9 ans, alors quil existe des signes de risque
accru chez les enfants srongatifs de <9 ans.32, 42
41
GRADE Table 4. See footnote 32. 41
Tableau GRADE 4. Voir note de bas de page 32.
42
Smith P. Dengue vaccine clinical trial results. Meeting of the Strategic Advisory 42
Smith P. Dengue vaccine clinical trial results. Meeting of the Strategic Advisory Group of Experts
Group of Experts (SAGE) on Immunization, 2016, Geneva, Switzerland. Available at (SAGE) on Immunization, 2016, Geneva, Switzerland. Disponible ladresse: http://www.who.
http://www.who.int/entity/immunization/sage/meetings/2016/april/2_Smith_Clini- int/entity/immunization/sage/meetings/2016/april/2_Smith_Clinical_Trial_Results_SAGE.pdf.
cal_Trial_Results_SAGE.pdf
43
Crevat D, et al. First Experience of Concomitant Vaccination Against Dengue and 43
Crevat D, et al. First Experience of Concomitant Vaccination Against Dengue and MMR in Tod-
MMR in Toddlers. Pediatr Infect Dis J. 2015;34(8):884-92. dlers. Pediatr Infect Dis J. 2015;34(8):884-92.
360 WEEKLY EPIDEMIOLOGICAL RECORD, NO 30, 29 JULY 2016
settings (seroprevalence 70% at 9 years), where the lence 70% 9 ans), o les modles prvoient une baisse de
reduction in symptomatic and hospitalized dengue 10% 30% du nombre de cas de dengue symptomatique et
predicted by the models ranged from 10% to 30% over dhospitalisations pour dengue sur une priode de 30 ans.
the 30-year period.
All models predicted that in very low transmission Tous les modles ont prdit que dans les contextes trs faible
intensity settings (seroprevalence 10% at 9 years) vacci- transmission (sroprvalence de 10% 9 ans), la vaccination
nation of 9 year-olds was likely to increase dengue des enfants de 9 ans entranerait probablement une augmenta-
hospitalization rates. Some models predicted the same tion des taux dhospitalisation pour dengue. Certains modles
effect when seroprevalence at 9 years was 30%. This was ont prdit le mme effet pour une sroprvalence de 30%
due to a key assumption used in the models, that vacci- 9 ans. Cela sexplique par une hypothse de base de ces modles,
nation acts like an asymptomatic natural infection and selon laquelle la vaccination sapparente une infection natu-
hence primes seronegative recipients to have a second- relle asymptomatique, rendant donc les sujets srongatifs
ary-like infection when they are exposed to dengue for susceptibles de prsenter une infection assimilable une surin-
the first time. In low transmission settings, where a high fection lorsquils sont exposs pour la premire fois au virus
proportion of the population never experiences a de la dengue. Dans les contextes de faible transmission, o une
second dengue virus infection, vaccination could there- forte proportion de la population ne contracte jamais de
fore lead to an increase in the incidence of dengue seconde infection par le virus de la dengue, la vaccination pour-
illness. The assumption on which this conclusion is rait donc accrotre lincidence de la dengue. Lhypothse sur
based cannot be confirmed or refuted by the clinical laquelle se fonde cette conclusion ne peut pas tre confirme
trial data collected to date, but it allows the models to ou dmentie par les donnes recueillies ce jour dans le cadre
match the currently available trial data. des essais cliniques, mais elle permet aux modles de se confor-
mer aux donnes dessai actuellement disponibles.
44
World Health Organization. Global vaccine safety blueprint. Available at http://ex- 44
World Health Organization. Global vaccine safety blueprint. Disponible ladresse: http://extra-
tranet.who.int/iris/restricted/bitstream/10665/70919/1/WHO_IVB_12.07_eng. net.who.int/iris/restricted/bitstream/10665/70919/1/WHO_IVB_12.07_eng.pdf?ua=1
pdf?ua=1
362 WEEKLY EPIDEMIOLOGICAL RECORD, NO 30, 29 JULY 2016
current labelling. The target age for routine vaccination actuel. Il revient chaque pays de dfinir lge cible de la vacci-
should be defined by each country, based on maximiz- nation systmatique en tenant compte des possibilits dopti-
ing vaccination impact and programmatic feasibility of misation de limpact et de la faisabilit programmatique du
targeting specific age groups.45 Some countries may ciblage de tranches dges spcifiques.45 Il est ainsi possible que
experience the highest incidence of dengue illness certains pays enregistrant une incidence particulirement
among adults and may consider vaccinating popula- leve de la dengue chez les adultes envisagent une vaccination
tions up to 45 years of age in routine programmes. systmatique jusqu lge de 45 ans.
Introduction of a routine CYD-TDV vaccination On estime que la mise en place dun programme de vaccination
programme at 9 years of age in settings meeting the systmatique par le CYD-TDV lge de 9 ans dans les contextes
criteria outlined above is expected to result in a rpondant aux critres cits ci-dessus devrait entraner une
10%30% reduction in symptomatic and hospitalized baisse de 10%-30% du nombre de cas de dengue symptomatique
dengue illness over 30 years. Catch-up campaigns et dhospitalisations pour dengue sur une priode de 30 ans.
targeting older age groups may be considered if addi- On pourra envisager des campagnes de rattrapage auprs de
tional impact is desired and the additional costs can be groupes plus gs si un impact plus important est recherch et
met, although most models predicted that a one-off si les cots supplmentaires peuvent tre couverts. Toutefois, la
catch-up campaign for children aged 917 years majorit des modles prdisent quune campagne de rattrapage
prevented a similar number of symptomatic and hospi- ponctuelle chez les sujets gs de 9 17 ans permettrait de
talized dengue cases per dose of vaccine delivered as prvenir un nombre de cas de dengue symptomatique et dhos-
in a routine vaccination programme at 9 years of age.40 pitalisations comparable, par dose de vaccin administr, celui
dun programme de vaccination systmatique 9 ans.40
Because the risk of immunological interference due to Les risques dinterfrence immunologique lis ladministra-
co-administration of live with non-live vaccines is tion concomitante de vaccins vivants et non vivants tant jugs
considered small, co-administration is permissible with faibles, la coadministration du CYD-TDV avec ces vaccins et
these and other non-live attenuated vaccines. Co-admin- dautres vaccins attnus non vivants est possible. La coadmi-
istration may be desirable to reduce programmatic nistration peut tre souhaitable pour rduire les cots program-
costs associated with school-based vaccination matiques associs la vaccination en milieu scolaire.46
programmes.46
CYD-TDV has not been studied as an intervention for Aucune tude na t mene sur lutilisation du CYD-TDV titre
dengue outbreak control. Although the 3-dose vaccine dintervention de riposte en cas de flambe de dengue. Bien
may be introduced during an outbreak as part of an quune vaccination 3 doses puisse tre mise en place lors
overall dengue control strategy, vaccination is not dune flambe dans le cadre dune stratgie globale de lutte
expected to have a significant impact on the course of contre la dengue, on ne peut escompter deffets significatifs de
the ongoing outbreak. Any deployment of the vaccine cette vaccination sur lvolution de la flambe en cours. Tout
in the context of an outbreak should only be done in dploiement du vaccin en situation de flambe devra se limiter
areas that meet the recommended seroprevalence crite- aux zones rpondant aux critres de sroprvalence recomman-
ria for introduction of dengue vaccine in routine ds pour lintroduction du vaccin dans le programme de vacci-
programmes. nation systmatique.
There is presently no recommendation concerning Aucune recommandation na t tablie ce jour concernant
CYD-TDV in pregnant and lactating women due to lack ladministration du CYD TDV aux femmes enceintes et allai-
of sufficient data in this population. However, the tantes, car on ne dispose pas de donnes suffisantes dans cette
limited data collected during the clinical trials on inad- population. Cependant, les donnes limites recueillies sur les
vertent immunization of pregnant women have yielded femmes enceintes vaccines par inadvertance durant les essais
no evidence of harm to the fetus or pregnant woman.32 cliniques nont rvl aucun prjudice pour le ftus ou la
Women of child-bearing age who are targeted for vacci- femme enceinte.32 Il nest pas ncessaire de faire subir des tests
nation do not need to be tested for pregnancy. de grossesse aux femmes en ge de procrer vises par la vacci-
nation.
Until data become available from forthcoming studies En attendant les rsultats dtudes venir chez les sujets infec-
in HIV-infected individuals or other persons with ts par le VIH ou dautres personnes immunodprimes, aucune
immune deficiency, there is no recommendation recommandation nest mise quant lutilisation du CYD-TDV
concerning the use of CYD-TDV in HIV-infected or dans cette population. Aucune recommandation na t formu-
immunocompromised individuals. There is no recom- le pour linstant concernant la vaccination des voyageurs ou
mendation for vaccination of travellers or health-care des agents de sant.
workers at this time.
45
For highly endemic settings (e.g. seroprevalence at 9 years of age of approximately 45
Dans les situations de forte endmicit (par exemple une sroprvalence 9 ans slevant
90% or greater), modelling predicts vaccination at 9 years of age will maximize environ 90% ou plus), les modles prdisent quune vaccination lge de 9 ans permet un
programme impact. In settings where seroprevalence at 9 years of age is between impact programmatique maximal. Dans les contextes o la sroprvalence lge de 9 ans se
50% and 90%, higher impact may be achieved with vaccination at 1114 years of trouve entre 50% et 90%, il est possible que limpact soit plus important si la vaccination a lieu
age. entre 11 et 14 ans.
46
See Administration of multiple injectable vaccines in a single visit in Meeting of 46
Voir Administration en une seule visite de plusieurs vaccins injectables, Runion du Groupe
the Strategic Advisory Group of Experts on immunization, April 2015: conclusions stratgique consultatif dexperts sur la vaccination, avril 2015: conclusions et recommanda-
and recommendations. Wkly Epidemiol Rec. 2015;90(22):261278. tions. Relev pidmiologique hebdomadaire 2015;90(22):261278.
RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 30, 29 JUILLET 2016 363
Dengue surveillance should be strengthened, particu- Il importe de renforcer la surveillance de la dengue, en parti-
larly in the context of emerging infections with clinical culier en prsence dinfections mergentes prsentant des simi-
similarities to dengue and in areas of the world for litudes cliniques avec la dengue et dans les rgions du monde
which data are scarce or absent. Use of standardized o les donnes sont rares ou inexistantes. Il est recommand
case definitions is encouraged to enhance data sharing dappliquer des dfinitions de cas standardises pour favoriser
and comparability across regions. With the increase in lchange et la comparabilit des donnes entre les rgions.
false-positive results from serological testing of CYD- Compte tenu du nombre croissant de rsultats faussement posi-
TDV vaccinated individuals,47 diagnostic testing should tifs des tests srologiques raliss chez les personnes vaccines
move to virological confirmation whenever possible. par le CYD-TDV,47 il est recommand de faire voluer les
mthodes de diagnostic pour les fonder si possible sur la confir-
mation virologique.
Important research and implementation questions Dimportantes questions persistent concernant la recherche sur
remain for CYD-TDV. Research on reduced or shorter le CYD-TDV et la mise en uvre de la vaccination. Une priorit
interval dosing schedules and safety in pregnant women leve doit tre accorde aux travaux de recherche portant sur
are high priorities. An approach to evaluate epidemio- la rduction ou la contraction des intervalles du calendrier
logic data based on high-quality age-stratified surveil- vaccinal, ainsi que sur la scurit du vaccin chez la femme
lance is needed to infer likely seroprevalence by age in enceinte. Il importe de dfinir une mthode dvaluation des
order to target vaccination efforts where seroprevalence donnes pidmiologiques issues dune surveillance de qualit
data are not available. As the vaccine is introduced in stratifie selon lge pour dterminer la sroprvalence probable
endemic countries, determination of vaccine effective- en fonction de lge, ce qui permettra de mieux cibler les efforts
ness by dose and duration of protection and long-term de vaccination lorsque les donnes de sroprvalence ne sont
impact of vaccine programmes will be research priori- pas disponibles. mesure que le vaccin sera introduit dans les
ties. However, it should be noted that using surveillance pays dendmie, la priorit sera accorde la recherche sur
data to monitor population impact of a vaccination lefficacit vaccinale selon la dose, sur la dure de protection et
programme may be challenging as the year-to-year vari- sur limpact long terme des programmes de vaccination. Il
ability in dengue virus transmission may be greater convient toutefois de noter que lutilisation des donnes de
than the expected vaccine impact on dengue illness. surveillance pour suivre limpact des programmes de vaccina-
Special studies should be conducted to monitor the tion sur la population peut prsenter de relles difficults, la
occurrence over time of severe dengue illness in vacci- variabilit de la transmission de la dengue dune anne lautre
nated persons, particularly among vaccinated seronega- pouvant tre plus importante que limpact attendu du vaccin
tive persons. ! sur la maladie. Des tudes spciales visant surveiller la surve-
nue de la dengue svre chez les personnes vaccines au cours
du temps, en particulier parmi les sujets srongatifs vaccins,
devraient tre menes. !
47
Plennevaux E, et al. Detection of dengue cases by serological testing in a dengue Plennevaux E, et al. Detection of dengue cases by serological testing in a dengue vaccine effi-
47
vaccine efficacy trial: Utility for efficacy evaluation and impact of future vaccine cacy trial: Utility for efficacy evaluation and impact of future vaccine introduction. Vaccine.
introduction. Vaccine. 2016;34(24):27072712. 2016;34(24):27072712.
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