How to make diagnostics for (re-)emerging virusesavailable in the affected regions?

ICREID MEETINGADDIS ABABA, ETHIOPIA14 MARCH 2019LIESELOTTE CNOPS

L. CNOPS

Disclosure statement

I have no potential conflict of interest to report.

L. CNOPS

4

STORY 1: development of a Ebola Dx test

2013-2016 Ebola outbreak in West Africa

August 4, 2014WHO: declared the Ebola outbreak a Public Health

Emergency of International Concern (PHEIC)

FDA Emergency use authorizationWHO Emergency use authorization list

1st case Europe/US

PHEIC

Guinea, Liberia, Sierra Leone DR Congo

Accelerated development of Ebola Dx tests

Oct 2014: FIND identified over 75 companies with assays in some stage of development.In total: 14 approved by FDA/WHO

Test nr

PCR-based Ebola virus test Company FDA EUA WHO EUAL Test type Target Virus

1 EZ1 Real-time RT PCR assay DoD Yes No PCR kit GP gene EBOV

2 Ebola Virus NP Real-time RT-PCR CDC Yes No PCR kit NP gene EBOV

3 Ebola Virus VP40 Real-time RT-PCR CDC Yes No PCR kit VP40 gene EBOV

4 FilmArray NGDS BT-E Assay Biofire Defense Yes No PCR all-in-one L gene EBOV

5 FilmArray Biothreat-E test Biofire Defense Yes No * PCR all-in-one L gene EBOV

6 RealStar® Ebola virus RT-PCR Kit Altona Diagnost Yes Yes PCR kit L gene EBOV, SUDV, BDBV, RESTV TAFV

7 LightMix® EBOV rRT-PCR Test Roche Yes No PCR kit L gene EBOV

8 Xpert® Ebola Assay Cepheid Yes Yes PCR all-in-one GP and NP gene EBOV

9 Liferiver™ Ebola Virus RT-PCR ShanghaiZJ BioTe No Yes PCR kit NP gene EBOV, SUDV, BDBV, TAFV

10 Idylla™ Ebola Virus Triage Test Biocartis Yes No PCR all-in-one GP gene EBOV, SUDV

Test nr

Antigen-based Ebola virus test Company FDA EUA WHO EUAL Test type Target Virus

11 ReEBOV™ Antigen Rapid Test Kit Corgenix/Zalgen No * No * RDT VP40 protein EBOV, SUDV, BDBV

12 OraQuick® Ebola Rapid Ag Test Orasure Yes Yes RDT VP40 protein EBOV, SUDV, BDBV

13 SD Q Line Ebola Zaire Ag SD Biosensor No Yes RDT NP, GP, VP40 protein EBOV

14 DPP Ebola Antigen System Chembio Diagnos Yes No RDT+ portable device VP40 protein EBOV

Cnops et al. 2016, Lancet ID

Idylla™ Rapid Ebola Virus Triage Test

Real time PCR-based nucleic acid detection

Sample in – result out (90 min)

EBOV + SUDV

FDA Emergency Use Authorisation in 2016

Cnops et al., 2016 (J Infect Dis)

Two years later…

Ministère de la Santé de la République Démocratique du Congo

EVD outbreak in DR Congo

Test nr

PCR-based Ebola virus test Company FDA EUA WHO EUAL Test type Available in 2 weeks Used in the DR Congo outbreak

1 EZ1 Real-time RT PCR assay DoD Yes No PCR kit no no

2 Ebola Virus NP Real-time RT-PCR CDC Yes No PCR kit no no

3 Ebola Virus VP40 Real-time RT-PCR CDC Yes No PCR kit no no

4 FilmArray NGDS BT-E Assay Biofire Defense Yes No PCR all-in-one no no

5 FilmArray Biothreat-E test Biofire Defense Yes No * PCR all-in-one no no

6 RealStar® Ebola virus RT-PCR Kit Altona Diagnost Yes Yes PCR kit yes no

7 LightMix® EBOV rRT-PCR Test Roche Yes No PCR kit yes no

8 Xpert® Ebola Assay Cepheid Yes Yes PCR all-in-one yes yes

9 Liferiver™ Ebola Virus RT-PCR ShanghaiZJ BioTe No Yes PCR kit yes no

10 Idylla™ Ebola Virus Triage Test Biocartis Yes No PCR all-in-one no no

Test nr

Antigen-based Ebola virus test Company FDA EUA WHO EUAL Test type Available in 2 weeks Used in the DR Congo outbreak

11 ReEBOV™ Antigen Rapid Test Kit Corgenix/Zalgen No * No * RDT no no

12 OraQuick® Ebola Rapid Ag Test Orasure Yes Yes RDT no yes

13 SD Q Line Ebola Zaire Ag SD Biosensor No Yes RDT no no

14 DPP Ebola Antigen System Chembio Diagnos Yes No RDT+ portable device no no

Many ebola Dx tests: no longer available, two years after the West African outbreak…

Test nr

PCR-based Ebola virus test Company FDA EUA WHO EUAL Test type Available in 2 weeks Used in the DR Congo outbreak

1 EZ1 Real-time RT PCR assay DoD Yes No PCR kit no no

2 Ebola Virus NP Real-time RT-PCR CDC Yes No PCR kit no no

3 Ebola Virus VP40 Real-time RT-PCR CDC Yes No PCR kit no no

4 FilmArray NGDS BT-E Assay Biofire Defense Yes No PCR all-in-one no no

5 FilmArray Biothreat-E test Biofire Defense Yes No * PCR all-in-one no no

6 RealStar® Ebola virus RT-PCR Kit Altona Diagnost Yes Yes PCR kit yes no

7 LightMix® EBOV rRT-PCR Test Roche Yes No PCR kit yes no

8 Xpert® Ebola Assay Cepheid Yes Yes PCR all-in-one yes yes

9 Liferiver™ Ebola Virus RT-PCR ShanghaiZJ BioTe No Yes PCR kit yes no

10 Idylla™ Ebola Virus Triage Test Biocartis Yes No PCR all-in-one no no

Test nr

Antigen-based Ebola virus test Company FDA EUA WHO EUAL Test type Available in 2 weeks Used in the DR Congo outbreak

11 ReEBOV™ Antigen Rapid Test Kit Corgenix/Zalgen No * No * RDT no no

12 OraQuick® Ebola Rapid Ag Test Orasure Yes Yes RDT no yes

13 SD Q Line Ebola Zaire Ag SD Biosensor No Yes RDT no no

14 DPP Ebola Antigen System Chembio Diagnos Yes No RDT+ portable device no no

Courtesy of Dr. Placide Mbala-Kingebeni

Test nr

PCR-based Ebola virus test Company FDA EUA WHO EUAL Test type Available in 2 weeks Used in the DR Congo outbreak

1 EZ1 Real-time RT PCR assay DoD Yes No PCR kit no no

2 Ebola Virus NP Real-time RT-PCR CDC Yes No PCR kit no no

3 Ebola Virus VP40 Real-time RT-PCR CDC Yes No PCR kit no no

4 FilmArray NGDS BT-E Assay Biofire Defense Yes No PCR all-in-one no no

5 FilmArray Biothreat-E test Biofire Defense Yes No * PCR all-in-one no no

6 RealStar® Ebola virus RT-PCR Kit Altona Diagnost Yes Yes PCR kit yes no

7 LightMix® EBOV rRT-PCR Test Roche Yes No PCR kit yes no

8 Xpert® Ebola Assay Cepheid Yes Yes PCR all-in-one yes yes

9 Liferiver™ Ebola Virus RT-PCR ShanghaiZJ BioTe No Yes PCR kit yes no

10 Idylla™ Ebola Virus Triage Test Biocartis Yes No PCR all-in-one no no

Test nr

PCR-based Ebola virus test Company FDA EUA WHO EUAL Test type Available in 2 weeks Used in the DR Congo outbreak

11 ReEBOV™ Antigen Rapid Test Kit Corgenix/Zalgen No * No * RDT no no

12 OraQuick® Ebola Rapid Ag Test Orasure Yes Yes RDT no yes

13 SD Q Line Ebola Zaire Ag SD Biosensor No Yes RDT no no

14 DPP Ebola Antigen System Chembio Diagnos Yes No RDT+ portable device no no

Cnops et al. 2019 Nature

But there is more than ebola…Recent arbovirus & VHF outbreaks in AFRICA JAN - FEB 2019(ProMed, WHO, CDC,…)

15

STORY 2: development of a multiplex tropical fever Dx test

Idylla™ Tropical Fever panel

Dengue 1 (DENV1)

Dengue 2 (DENV2)

Dengue 3 (DENV3)

Dengue 4 (DENV4)

Chikungunya virus (CHIKV)

Yellow fever virus (YFV)

Tickborne enceph virus (TBEV)

Japanese enceph virus (JEV)

West Nile virus (WNV)

Zika virus (ZIKV)

P. falciparum

P. ovale

P. vivax

P. malariae

Controls

ICREID meeting 2018: potentialof the tropicalfever multiplex PROTOTYPE test

Courtesy of Rudi Pauwels (Praesens)

WHY??cost is highcommercial interest for infectious diseases is low (no market?)need another 2-5 years (?) for commercialisation (evalutions, regulatoryapprovals,…) before roll-out can be initiated

COMPANIES: need incentives to justify these costs

TOO LONG: need to accelerate this process as part of epidemic preparedness

But today…ANNO 2019?

NO COMMERCIALISATION of the tropical fever multiplex test…

22

SOLUTIONS?

1) How to tackle the low interest for commercialisation by companies?

create ‘market’ (surveillance)

Incentives for developers (funding)

2) How to accelerate and ensure sustained availability in affected regions?

Integrated diagnostic approach (bringing key stakeholders together)

!! CALL FOR ACTION !!

IMPACT of surveillance: the example of Uganda

Shoemaker et al. 2018 Lancet

2010

Significant DECREASE in intensity and duration of VHF outbreaks in Uganda (20 sentinel sites) EVD, MARV, CCHF, RVF

4S (Senegalese Sentinel Syndromic Surveillence)

Sow et al. 2016 Malaria J

Africa CDC: engagement forstrengthening health systems

Laboratory networks:

(LABNET, RESAOLAB,…)

Surveillance systems:

(GLASS, RISLNET, AMRSNET,…)

Integrated surveillance initiatives in AFRICA

Amukele T, 2017 (African J LabMed)

Nkengasong et al., 2017 (The Lancet)

Valley of death between Dx test development and commercialization

Startups That Died Reveal Why They Failed (www. business insider.com)

Sustained investment in diagnostics

Dx forEpidemicpreparednessOutbreakstrategy 2018

US$ 65 million/5 years

According to the World Bank, Africaneeds between US$2 billion and $3.5 billion a year for epidemic preparedness

Bringing togetherkey stakeholders

Together with partners in theworld of vaccins

Implementation of Dx tests in the field: there where they are NEEDED!

Selection of the Dx test: prioritization

Rapidly available (outbreak)

Sustained availibility (surveillance)

How will coordinate all this?

Most importantly…

GLOBAL DIAGNOSTIC ALLIANCE

38

CONCLUSION

Companies, Governments, International health organizations, Laboratory networks, Research institutes

GLOBAL DIAGNOSTIC ALLIANCE

design/research development validation implementationManufacturing/

stockpilingsurveillance

MAKING diagnostics for (re-)emerging viruses available in the affected regions!!

Steve Ahuka-Mundeke, INRB

Placide Mbala-Kingebeni, INRB

Kevin Ariën, ITM

Birgit De Smet, ITM

Johan van Griensven, ITM

Acknowledgements

Rudi Pauwels

Steven Pauwels

Aurélie Cappuyns

Amadou Sall

Oumar Faye

Cheikh Fall

Lot Cnops lcnops@itg.be