Le virus Monkeypox : épidémiologie et évolution
Federica Palma1 et Sylvain Brisse1,2,*
Membres du comité de Direction de la Section Epidémiologie et Génomique des Populations de la SFM
1 Centre de Ressources Biologiques de l’Institut Pasteur, Institut Pasteur, Université Paris Cité, Paris
2 Unité Biodiversité et Epidémiologie des Bactéries Pathogènes, Institut Pasteur, Université Paris Cité, Paris
* sbrisse@pasteur.fr
Qu’est-ce que le virus de la variole du singe, ou monkeypox ?
La variole du singe est une infection zoonotique, qui peut se propager par transmission interhumaine. Considérée endémique dans une dizaine de pays d’Afrique occidentale et centrale, cette maladie peut toucher le reste du monde via des cas importés. L’agent responsable est le virus de la variole du singe, un virus à ADN double brin enveloppé qui appartient à la famille des Poxviridae, à la sous-famille des Chordopoxvirinae et au genre Orthopoxvirus. Ce genre comprend également le virus de la variole (responsable de la variole, ou smallpox) (Bunge et al., PLoS Negl Trop Dis). Étant étroitement apparenté au virus variolique, le virus de la variole du singe se traduit par une maladie semblable (mais moins transmissible et moins grave) à celle de la variole. Cependant, à la différence du virus de la variole, qui n’infecte que les humains et a ainsi pu être éradiqué suite à la vaccination massive de la population mondiale, le monkeypox a un réservoir animal.
D’où vient ce virus et le nom monkeypox
Bien que le réservoir naturel du virus de la monkeypox reste mal connu, les rongeurs et les primates non humains peuvent héberger le virus et infecter l’homme. Ce virus a été découvert pour la première fois en 1958 dans un laboratoire danois, lorsque deux épidémies ressemblant à la variole sont apparues chez des singes élevés à des fins de recherche, d’où le nom monkeypox (von Magnus Acta Path Microbiol Scand).
Transmission chez l’homme
Le premier cas chez l’homme a été diagnostiqué en 1970 en République Démocratique du Congo (Breman et al., Bull World Health Orga). Depuis lors, la variole du singe est considérée endémique en RDC et dans certains pays d’Afrique centrale et occidentale (ex. Gabon, Côte d’Ivoire, Liberia, Nigeria…). En 2017, le Nigeria a connu une des plus importantes épidémies, avec plus de 500 cas suspects et plus de 200 cas confirmés et un taux de létalité d’environ 3 %.
Le virus se transmet d’une personne à l’autre par contact étroit avec des lésions, des fluides corporels, ou des gouttelettes respiratoires, qui nécessite généralement un contact prolongé. La transmission peut également se faire par les muqueuses d’animaux infectés, le placenta de la mère au fœtus (ce qui peut entraîner une variole congénitale) ou lors de contacts étroits pendant et après la naissance. Si le contact physique étroit est un facteur de risque bien connu de transmission, le risque de transmission par voie sexuelle est en cours d’étude (OMS).
La propagation du virus en dehors de l’Afrique
En dehors de l’Afrique, le virus était rarement signalé et notamment lié à des voyages internationaux ou à des animaux importés. Les premiers cas de variole du singe qui ont été signalés en dehors d’Afrique, aux États-Unis, remontent au 2013. Depuis, des cas ont été signalés en 2018-2019 en Israël, à Singapour et au Royaume-Uni.
En mai 2022, plus de 300 cas de monkeypox ont été identifiés dans plusieurs pays européens, tels que le Royaume-Uni, le Portugal, l’Espagne, la France, l’Italie, l’Allemagne, la Suède, la Belgique, ainsi qu’aux États-Unis, Canada et Australie. A ce jour, mardi 7 juin, le nombre de cas répertoriés par l’OMS à travers 27 pays non endémiques est plus que doublé et dépasse les 50 en France (https://ourworldindata.org/monkeypox). Bien que d’autres études soient en cours pour mieux comprendre l’introduction et l’émergence rapide du monkeypox dans ces pays, l’OMS estime le risque de cette épidémie au niveau mondial comme modéré pour la santé publique.
Émergence récente du virus: faut-il s’inquiéter ?
L’une des principales préoccupations est que l’émergence récente du virus de la variole du singe est entourée de mystère. En effet, cette infection a été détectée chez des personnes n’ayant aucun lien apparent les unes avec les autres, laissant penser qu’il aurait pu se propager silencieusement, dit Andrea McCollum, épidémiologiste au CDC américain. “Une propagation asymptomatique du monkeypox serait particulièrement inquiétante car cela rendrait le virus plus difficile à dépister,”, précise-t-elle, “mais contrairement à la COVID19 qui peut se propager de manière asymptomatique, le monkeypox ne passe généralement pas inaperçu à cause des lésions cutanées qu’il provoque chez les infectés.”.
Si la maladie peut être grave chez les enfants et les immunodéprimés (surinfection des lésions cutanées ou d’atteintes respiratoires ou digestives), les nouveaux cas rapportés en mai 2022 sont majoritairement bénins, et il n’y a pas de décès signalé.
La plus longue chaîne de transmission documentée avant mai 2022 dans une communauté est passée de 6 à 9 infections successives de personne à personne. L’épidémie actuelle pourrait refléter une baisse de l’immunité en raison de l’arrêt de la vaccination antivariolique depuis son éradication dans les années 1980, ou tout simplement un effet d’aubaine du virus, qui aurait été propagé de manière inhabituelle à la faveur d’événements festifs de grande ampleur. Les études épidémiologiques sont en cours pour mieux comprendre la transmission de la souche actuelle. Dans tous les cas, le virus ne se transmet pas par aérosol comme le SARS-CoV-2, et le risque de pandémie est très limité voire nul selon les épidémiologistes.
Le variant du virus lié à l’épidémie actuelle
Il existe deux lignées génétiques distinctes du virus de la variole du singe : le clade d’Afrique centrale (bassin du Congo) et le clade d’Afrique occidentale. Le clade du bassin du Congo a historiquement causé une maladie plus grave et était considéré comme plus transmissible.
Au Portugal, qui avait déjà enregistré plus de 20 cas de variole du singe confirmés au 19 mai 2022, les premières séquences génomiques du virus monkeypox associées à l’épidémie actuelle ont été rapidement générées (5 jours entre identification et séquençage) et rendues publiques dans NCBI. Ensuite, plus de 20 pays ont généré et partagé de séquences liées à l’épidémie actuelle. L’analyse phylogénétique préliminaire de ces séquences, en comparaison avec des données génomiques déjà disponibles, a permis d’en décrire la microévolution et la diversité génétique du virus qui émerge actuellement (Isidro et al., 2022):
- L’épidémie a très probablement une origine unique (les séquences sont étroitement similaires et regroupées en une branche unique dans l’arbre).
- Le virus de l’épidémie appartient au clade d’Afrique occidentale et est le plus étroitement lié aux virus associés à l’exportation du virus monkeypox du Nigeria vers le Royaume-Uni, Israël et Singapour en 2018 et 2019.
- Pourtant, le virus de l’épidémie diverge en moyenne de 50 mutations par rapport au virus de 2018-2019, ce qui est considérable étant donné le taux évolutif estimé pour les orthopoxvirus, de 1 à 2 mutations par an par génome de 200 000 nucléotides. Cela suggère que la divergence de ces souches avec les autres séquences répertoriées n’est pas très récente.
- On observe des premiers signes de microévolution au sein du cluster de l’épidémie, avec 7 mutations conduisant à des branches descendantes, dont un sous-groupe qui partage une délétion de 913 bp entraînant un décalage du cadre de lecture (frameshift) dans un gène codant pour la protéine ankyrine, liée au spectre d’hôte . La perte de gènes, déjà observée dans le contexte de la circulation endémique de la variole du singe en Afrique centrale, est possiblement associée à la transmission interhumaine.
Le séquençage plus systématique du génome des isolats viraux à l’origine de ces nouvelles infections est en cours et contribuera certainement à mieux en comprendre l’épidémiologie, les sources d’infection et les modes de transmission.
L’arbre phylogénétique mis à jour avec les nouvelles séquences est disponible ici : https://nextstrain.org/monkeypox?tl=country (Figure).
Qu’en est-il des vaccins ?
Nous ne sommes pas impuissants face à la variole du singe. Des réserves de vaccins contre la variole, ainsi qu’un traitement antiviral considéré comme très efficace contre le virus, sont disponibles aujourd’hui dans de nombreux pays.
Des données historiques indiquent que la vaccination antivariolique offrirait une protection d’environ 85 % contre la variole du singe. Cependant, ces données sont anciennes et limitées.
Sur la base des données disponibles, les scientifiques assurent que l’épidémie actuelle ne nécessite pas de stratégies de contrôle autre que le dépistage et la vaccination ciblée, ou vaccination en anneau : vacciner les contacts proches des personnes infectées (et le personnel soignant) afin de rompre la transmission.
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