Chikungunya: An emerging outbreak from East Africa to Indian Ocean,

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1 Chikungunya: An emerging outbreak from East Africa to Indian Ocean, A. Flahault, G. Aumont, V Boisson, X de Lamballerie, F. Favier, B.A. Gaüzère, D. Fontenille, S. Journeaux, V. Lotteau, C. Paupy, M.A. Sanquer, M. Setbon French Task Force on Research on Chikungunya

2 La Réunion, 2006 (785,000 inhab.) A previously unknown case mix cases Nombre de décès death certificates 90 with "chikungunya" transmissions in 150 newborns 60 Effectif % of cases were hospitalised cases in ICU, deaths Gravité de la maladie Médiane = 8 Moyenne =7,7875 Ecart type =2,03086 N =1 021 [0-5] [6-15] [16-30] [31-45] [46-60] [61-75] [76-90] > 90 Classes d'âge (en années)

3 Chikungunya as a model? a poorly known arbovirosis a disease - rarely severe - but affecting 40% of a population in highly developped countries as well as less developped neighbours => an interesting model for monitoring and research on emerging diseases

4 10/ /2004 : 75% 03/ /2005 : 63% 01/2005 : 40%?/ / /2005 : 38%

5 Two epidemic waves? S9 S11 S13 S15 S17 S19 S21 S23 S25 S27 S29 S31 S33 S35 S37 S39 S41 S43 S45 S47 S49 S51 S1 S3 S5 S7 S9 S11 S13 S15 S17 S19 S21 S23 S25 S ? 2006

6 Sequencing genome of chikungunya virus Indian Ocean : 92 sequences from 89 patients Date Sequences A226 V226 March to June September to December January to March Switch from A226 to V226 between the 2 epidemic waves From Schuffenecker I et al, PLoS Medicine 2006

7 Two waves but a single epidemic force Boelle and Flahault, Vect Born Zoon Dis, < R < 4 Week Reproduction number Incidence

8 Prevention & control Extensive sequencing, ORFeome, Interactome Diagnostic tests and seroprevalence surveys diagnostic kits (serology, RT-PCR,...) Treatments Screening for antiviral properties in already marketed drugs R&D for new antiviral drugs Immunotherapies polyclonal antibodies monoclonal antibodies classical or chimeric vaccines Pest control insecticides Genetically modified insects, sterile males (irradiated), infected males (who sterilize females)

9 Social sciences: beliefs vis-à-vis routes of transmissions Les croyances sur les modes de contamination Strong disagreement Total Agreement Human-to-Human Contacts humains transmission 53,4 12,7 13,5 20,4 Airborne transmission Virus dans l'air 52,9 10,6 16,7 19,8 Mosquito Moustiques 77 % 10,7 12,5 21,0 55,7 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Pas du tout d'accord Plutôt pas d'accord Plutôt d'accord Tout à fait d'accord

10 Understanding social beliefs Les croyances sur l'origine de l'épidémie Strong disagreement Total Agreement A ship in quarantine origine bateau 26,4 11,9 41,1 20,6 CIA - Americans origine CIA 56,6 16,6 18,4 8,4 Tsunami origine tsunami 50,9 16,1 23,9 9,2 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% pas du tout possible plutôt pas possible plutôt possible tout à fait possible pictures from B-A Gaüzère

11 Worldwide spread of Aedes albopictus From Charrel R et al. NEJM, 2007

12 Chloroquine is a potent inhibitor of CHIKV replication ex-vivo X. de Lamballerie, Unité des Virus Emergents, Marseille, mars 2006

13 Clinical Trials CuraChik : RCT chloroquine 600 mg/d x 3d then 300 mg/d x 2 vs placebo, double blind ; 250 pts interim analysis (Aug. 30, 2006) : 75 pts.

14 Macaque as an animal model Infection expérimentale Nombre absolu de cellules circulantes Charge virale plasmatique Log(eqTCID50) 1000 D1-D5: detectable viremia from 3 RT-PCR D2: fever, transcient swelling in joint D1-D3: diffuse eruption mild intensity lymphocytes Le Grand, Granulocytes D3-D5: 0 oedema 5 10 neck 15and sore 20 throat Monocytes Temps post infection (jours) Charge virale Le Grand, Aug

15 Animal experiments PrimaChik : prevention trial in 18 macaques in A3 animal lab settings (CEA, Gif-sur-Yvette) Nov Mar. 07 De Lamballerie X, Lotteau V, Aumont G, Le Grand, 2006

16 De Lamballerie X, Lotteau V, Aumont G, Le Grand, 2007

17 De Lamballerie X, Lotteau V, Aumont G, Le Grand, 2007

18 Monoclonal antibodies 2002: 30% of approved drugs Monoclonal Ab and recombinant proteins 2010: >90% of biotech turnover. 3 generations of monoclonal antibodies Chimeric Ab Humanised Ab Cloned Human Ab clonage-transformation-activation of B lymphocytes from a recovered chik patient

19 ORFeome - Interactome Extensive ORFeome of the virus clonage from coding sequences vectors to produce recombinant proteins -> monoclonal Ab Interactome Mapping protein interactions virus - host virus - virus Research and seeking for therapeutic targets Susceptibility factors or host resistance to severe forms

20 Chimeric vaccines Attach a viral segment which is responsible for a immune reaction but no disease to a viral vector which is not pathogenic identified from monoclonal Ab

21 A Centre for Monitoring and Research in Indian Ocean a long term objective 1. Appropriate time: need for answers to social and political demands, and to face fears for the future 2. Appropriate scientific aim: lack for knowledge on emerging diseases in an exposed area 3. Implementation by 2007 in La Réunion multidisciplinary highly scientific purpose international scope

22 Sanquer Lotteau Favier Setbon de Lamballerie Fontenille Journeaux Paupy Boisson Aumont Gaüzère Flahault Hervé La cellule de coordination des recherches sur la dengue et le Chikungunya La Réunion, Octobre 2006

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