Value of Diagnostics in Global health Security

Transcription

1 Value of Diagnostics in Global health Security Dr Amadou A SALL WHO Collaborating Center for Arboviruses and hemorrhagic fever viruses 1

2 Outline Background on Global Health Security Cases studies Way forward Take home messages 2

3 International Public Health Threat

4 Historical background 14th century: first use of quarantine to prevent bubonic plague from crossing borders 1969: International Health Regulation as global framework for health security against Plague, cholera, smallpox and yellow fever with action at the borders SARS epidemic lead to broadening scope of IHR and reporting of public health emergency of international concern 2007: Pandemic Influenza Preparedness framework «Equal benefit for equal sharing» 4

5 Health Security Two levels Collective level Individual level 5

6 International Health Regulation 2005 Paradigm shift From control of borders to containment at source From diseases list to all public health threats From preset measures to adapted responses

7 Public Health Emergency International Concern Public Health Emergency of International Concern (PHEIC ) an extraordinary event which is determined to constitute a public health risk to other States through the international spread of disease and to potentially require a coordinated international response. This definition implies a situation that is: - serious, sudden, unusual or unexpected; - carries implications for public health beyond the affected State s national border; and - may require immediate international action. 7

8 High political level involvement in outbreak diagnostics Dengue Cape Verde 2009 EVD Guinea Rift Valley Fever Mauritania 2010

9 Global health risk Emergence and spread of new microbes, especially zoonoses Rapid spread of diseases across borders due to travel, trade and the migratory patterns of animals Antimicrobial resistance Potential for accidental release, theft or illicit use of dangerous microbes 9

10 Global health security agenda Focus at 2 levels of action Strengthening health security and preparedness globally. Improving preparedness at country and regional levels, Objectives Prevent avoidable epidemics Detect threat early Respond rapidly and effectively 10

11 Number of Cases Emergence process Readiness Rapid Early Response Detection Amplification Control Opportunity TIME 11

12 EVD in West Africa: a public health emergency of international concern Data up to August

13 13 Infection and transmission routes

14 EVD outbreak: Timeline of events 6 October: First secondary case of Ebola outside Africa: Spain 14

15 Situation in Guinea December 2013 to September 2015 Phase II: Adapted strategy Phase I: response as usual Phase III: getting to Zero 15

16 Role of diagnostics laboratory during the outbreak Phase I Identify case to support response and control Phase II Identify case to support response and control Speed is critical Other parameters (viral load, biochemistry, hematology, electrolytes ) Diagnostics tools evaluation (diagnostic & surveillance) Phase III Identify case to support response and control Point of care and rapid Transmission chains identification Support cinical trial and research projects Diagnostics tools evaluation 16

17 Deployment and field evaluation of VHF diagnostics tests 1. Route from Dakar to field trip site at Kedougou (700km) 2. Kedougou field station 3. Laboratory at Kedougou field station on arrival 4. Dry PCR mixes: 4x screening mixes, 10x patient mixes, RNA positive controls 5. PCR flow line up : Extraction, PCR 1-3, cyclers at far end. 6. Extraction site 7. PCR 1 (mastermix) site 8. PCR 2 (samples meet mix) site 9. PCR 3 (positive controls) site 10. Mobile PCR-cyclers 11. Bandafasi health post 12. Bandafasi laboratory 13. Electricity source from vehicle provided through laboratory window 14. PCR flow in Bandafasi laboratory 15. Mobile PCR-cyclers in Bandafasi laboratory

18 RT-PCR for VHF Kedougou Dakar 18

19 Coordinated response against Ebola in Guinea Daily meeting at WHO Mobile laboratory installed at Donka Hopital Donka - Conakry Ebola Treatment Center - MSF Donka Hopital Conakry 19

20 Sampling from Conakry Ebola treamentsamples shipment to the laboratory Treatment center Sampling Exit from the patient ward Disinfection of sampling tubes Sampling in triple packaging Shipment to the lab 20

21 Activities for laboratory for Ebola viruses A B C 21

22 22 Social reticences

23 Development of RPA based rapid test

24 Field operating format Mobile glove box Lyophilized Mix SpeedExtract (10-15 min) Generator power With solar panel TubeScanner 24

25 Deployment in the field in Guinea IPD Point of care diagnostic testing for Ebola virus disease in Matoto District, 28 March Guinea Conakry

26 Commercial, in house, rapid tests evaluation Prequalification process Emergency Use Authorization Biobanking Access to population Cost 26

27 Co-circulation of different lineages Gire, Science 2014 Hoenen, Science 2015 Kugelman, 27 EID 2015 Simon-Loriere, submitted 3 distinct lineages in the Conakry area: GIN 1, directly linked to the earliest viruses GIN 2, later found in Mali GIN 3-SLE3, reintroduced from Sierra Leone

28 Co-circulation of different virus lineages Gire, Science 2014 Hoenen, Science 2015 Kugelman, 28 EID 2015 Simon-Loriere et al, Nature distinct lineages in the Conakry area: GIN 1, directly linked to the earliest viruses GIN 2, later found in Mali GIN 3-SLE3, reintroduced from Sierra Leone

29 29 West Nile transmission cycle

30 Genetic diversity of West Nile virus Great genetic diversity: 8 lineages worldwide Biological features associated to the diversity to be investigated

31 Characterization of pathogenicity of West Nile lineages 31 STRAIN LIN NS3 249 VIRAL DOSES (pfu) DL50 KOUT RSA MO 03 1a Thr NY 99 (Exp 1) 1a Pro NY 99 (Exp 2) 1a SPA 07 1a FR 00 1a Thr IT08 CISA 1a Pro IT08 ANSES 1a ISR 98 1a AUS 08 2 His B956 2 His SEN n.a KUNJIN 1b n.a MALAYSIA n.a

32 Geographic distribution Previously endemic in Africa, Asia, Europe and Australia (Hubalek and Halouzka, 1999; Monath et al., 1983; King et al., 2007) Introduced in New York in 1999 followed by rapid propagation in America (Nash et al., 2001) Incidence per million >100 Any WNV Activity

33 33 West Nile virus geographic distribution

34 West Nile virus movements between Europe and Senegal Peak of ligneage 2 in 2003 Coincidental with occurrence in Europe in : epidemics in Europe, Morroco, Tunisia (with fatal encephalitis) Other local ligneages: importation to Europe, adaptation to new ecological niches or lineage replacement 34

35 Zoonotic pool of WN virus lineages? Zoonotic pool Different lineages of West Nile Emergence based on viral, entomological, environmental and human factors 35

36 West Nile RT-PCR screening and typing Sensitivity: 10 genomes copies 36

37 West Nile assay evaluation Specificity Strains Virus Threshold Cycle (Ct) Pan-Flavi WNV Consensus WNV Lineage 1 WNV Lineage 2 WNV Koutango Lineage WNV new Lineage Assay 1 Assay 2 Assay 1 Assay 2 Assay 1 Assay 2 Assay 1 Assay 2 Assay 1 Assay 2 Assay 1 Assay 2 Eg 101 WNV ArD WNV ArD76986 WNV B956 WNV ArD WNV ArD WNV ArD WNV ArD96655 WNVK AnD95153 WNVK ArD94343 WNV N New Guinea C Dengue H-241 Dengue ArAAMT/7 YF MR 766 Zika SAAR1776 Usutu ArB1803 Usutu ArD Bagaza

38 West Nile assay evaluation Performance on field and experimental samples Species Type of sample Virus WNV Lineage 1 WNV Lineage 2 WNV Koutango Lineage WNV new Lineage Assay 1 Assay 2 Assay 1 Assay 2 Assay 1 Assay 2 Assay 1 Assay 2 Field samples Culex quinquefasciatus Mosquito pool ArD Mastomys erythroleucus Rodent tissues AnD Experimental samples Culex quinquefasciatus Mosquito body ArD Mosquito legs/wings ArD Mosquito saliva ArD Mosquito body ArD Mosquito body B Culex neavei Mosquito body ArD Mosquito legs/wings ArD Mosquito saliva ArD Mosquito body ArD

39 Evolution influenza samples in Senegal national reference center H3N2 H1N1 B Reçus 0 39

40 Lessons Focus on needs of weakest countries and area Product development Capacitiy building Laboratory strengthening Quality Management System Surveillance and preparedness Not business as usual but on a case by case approach Sustainability Regional and national champions Research on disease Tools development Routine diagnostics Partnerships 40 Coordination

41 Way forward: Innovative surveillance approach Innovative surveillance approach Community surveillance and involvement Sentinel sites and observatoire of integrated surveillance (one health, environment and vectors) Real time and IT based infrastructure Gradual deployment Tiered system 41

42 Way forward: Innovative diagnostics Innovative diagnostics tools Predvelopment phase in collaboration with local stakeholders Community engagement to keep in mind Syndromic approach combined multipathogen, multiparameter Customized and flexible solution Molecular, IT and Point care 42

43 Way forward: Initiatives to Support Diagnostics Local production of In Vitro Diagnostics tools Financing model for sustainable funding of surveillance (HR, Diagnostics tools, Quality) 43

44 Take Home messages Ebola is a wake up call!!!! Keep in mind, Ebola is not gone and more other are waiting and coming Let us be mobilized after the outbreak Focus should be on the developing countries and Africa in particular Research Surveillance and public health Training Ownership by local players is critical 44

45 Acknowledgements Virology team at IP Dakar Ministry of Health of Guinea and Senegal WHO (CO, AFRO, HQ, GOARN ) Partners laboratories (EU, CDC, Winnipeg ) Medecins sans frontières M Weidmann, P Patel, M Niedrig; Ali Abdel Wahed Institut Pasteur and Institut Pasteur International Network JC Manuguerra, C Batejat S Cauchemez, A Sakuntabhai Task force members ASLM London School of Hygiene Tropical Medicine Fondation Merieux