Gavi Yellow Fever Diagnostic Initiative

Lee Hampton, MD, MSc 14 March 2019

Reach every child www.gavi.org Conflict of Interest Disclosure: Nothing to Disclose

2 Gavi Background

3 About Gavi

Gavi’s mission

Saving by increasing and protecting in lower-income children’s equitable use of people’s health countries lives vaccines Vaccine Alliance partners

IMPLEMENTING COUNTRY DONOR COUNTRY GOVERNMENTS GOVERNMENTS

CIVIL SOCIETY RESEARCH ORGANISATIONS AGENCIES

VACCINE PRIVATE MANUFACTURERS SECTOR PARTNERS About Gavi

The Gavi business model: reinventing aid

Pooling demand of Long-term Accelerating Shaping Strengthening vaccine Sustaining poorest countries funding access to vaccines markets delivery platforms immunisation

Market shaping Transition Country out of Country support Donor base Supply Demand Country Country

Country Co-financing Continued support Country Gavi’s resource mobilisation model: a three- pronged approach

3 increasing US$ 133m country co-financing

growing 1 donor $ contributions US$ US$ 32m 1,676m US$ 696m US$ 330m 2000 2010 2016 Yellow Fever and Laboratory Capacity

8 9 Eliminate Yellow Fever Epidemics (EYE) –2017-2026 EYE strategy aims to build a global coalition of countries and partners to tackle the increased risk of yellow fever epidemics • Targets 40 countries considered most vulnerable to YF outbreaks • 27 in the African region • Strategy based around 3 key strategic objectives 1)Protect at-risk populations 2)Prevent international spread 3)Contain outbreaks rapidly

• Scientifically validated by SAGE in Oct 2016; Gavi Board approval in Dec 2016 Gavi and Yellow Fever (YF)

Gavi board has approved up to US$ 428 million for yellow fever vaccine use during 2016-2020 • Routine immunization • Preventive mass campaigns • Outbreak reactive campaigns and vaccine stockpile Yellow fever outbreaks are a major problem • Outbreaks since 2015 include Angola, Brazil, DRC, Ethiopia, Nigeria, Republic of Congo and Uganda • 2016 DRC outbreak cost Gavi alone US$ 13.7 million • YF vaccine supply improving but finite Reliable YF diagnostic capacity can improve the impact and efficiency of YF vaccine investment • Yellow fever clinically similar to other diseases • Laboratory testing needed to distinguish it 10 Timely detection and response prevents death and disease – Case of Angola YF outbreak

Time Required for Identification Aggressive vaccination response & Laboratory estimated to have prevented over 360 Confirmation deaths and 5200 cases in Luanda alone of Outbreak Index Case

Source: Zhao et al, Modeling the Large-scale Yellow Fever Outbreak in Luanda, Angola, and the Impact of Vaccination, PLOS Neg Trop Dis, 2018, 12:e0006158.

11 More rapid yellow fever outbreak detection and response may allow more efficient vaccine use

25.000.000 Time Required for 20.000.000 Identification and Spread of Angola YF outbreak Laboratory to the Democratic Republic of Congo 15.000.000 Confirmation of Outbreak Index Case 10.000.000

5.000.000 Cumulative doses shipped Angola + DRC

Cumulative doses shipped Angola and DRC through ICG ICG through ProcessandDRC 0

05-dec 05-jan 05-feb 05-mrt 05-apr 05-mei 05-jun 05-jul 05-aug Cumulative YF Vaccine Doses Shipped to Angola toShipped Doses YF Vaccine Cumulative

12 Average time needed to confirm yellow fever highlights need to improve laboratory testing

National Sample Regional Sample National Laboratory received by Reference arrives to Laboratory positive Regional Laboratory National completes sample Reference completes Laboratory testing received by Laboratory testing courier

Avg. 11 Avg. 77 Avg. 2 Avg. 10 days days days days

0 20 40 60 80 100 Source: Based on site visits to Angola, Benin, Burkina Faso,, NUMBER OF DAYS Cameroon, CAR, Chad, Cote d’Ivoire, DRC, The Gambia, Niger, 13Sudan, and Togo Gavi Alliance assessments and stakeholder outreach have identified laboratory capacity gaps

Data Source Gaps - FIND yellow fever diagnostic - Validated, standardized YF test kits not market assessment available

- Yellow fever laboratory capacity - Frequent stockouts of critical reagents assessment - Limited national Quality Assurance / - Eliminating Yellow Fever Quality Control (QA/QC) testing Epidemics Laboratory Technical - Insufficient YF training Working Group - Sample transportation bottleneck - Laboratory capacity assessment - Lack of funding for YF testing supplies - Donor outreach and equipment

14 Gavi Support for Yellow Fever Diagnostic Laboratory Capacity

15 Stakeholders have identified potential solutions for which Gavi Alliance has comparative advantage

Problems Solutions Validated, standardized YF Tests Market shaping to encourage not available availability of validated YF test kits Many samples not tested due to Improved procurement of testing stockouts of critical reagents materials Limited QA/QC and proficiency Regular QA/QC, proficiency testing, testing, insufficient YF training technical assistance, and training Sample transportation bottleneck Facilitate intl. sample transportation Improve natl. confirmation capacity Lack of funding for YF testing Funding provided in such a way to supplies and equipment ensure financial sustainability

16 Changes in YF marker of infection require that both molecular and serology test kits be available

Waggoner JJ, Rojas A, Pinsky BA. 2018. Yellow fever virus: diagnostics 17 for a persistent arboviral threat. J Clin Microbiol 56:e00827-18. Through pooled procurement, Gavi hopes to create sufficient market pull for validated YF Dx test kits

Level of evidence needed to warrant laboratory network use and Gavi support Strongest level of evidence for currently available molecular (PCR) YF tests Strongest level of evidence for currently available serology YF tests 18 Sustainable financing to improve reliability in YF diagnostics

• Countries will eventually need to provide funding for YF diagnostic capacity and procurement Other • National governments already covering some donors core costs (e.g., staff, utilities, buildings) • Country co-financing will not be required initially: Gavi • Allow countries sufficient time to include co- financing amount in their budget cycles

National • Experience from other Gavi investments will be governments leveraged in developing a sustainable system • Gavi YF diagnostic laboratory capacity support will complement other laboratory strengthening efforts

19 Gavi Board approved US$ 13.5 million for 2019-2021

Diagnostic Procurement • Diagnostic equipment and US$ 8.2 million supplies

Laboratory Network • Technical assistance Capacity • QA/QC testing • Sample transportation US$ 5.3 million • Laboratory network coordination

Applies to African countries eligible for Gavi support at high risk for YF Countries can continue to use other Gavi funds for general laboratory capacity Yellow fever laboratory capacity included in Gavi country transition process

20 Gavi yellow fever diagnostic initiative focused but multifaceted Goal is to allow better targeting of YF vaccine use, particularly by improving timeliness and completeness of YF laboratory network testing Multiple partners are already involved, including: • WHO • Institut Pasteur Dakar • Centre Pasteur Cameroon • U.S. CDC • Uganda Viral Research Institute • FIND • National public health yellow fever laboratories • Erasmus MC • EYE laboratory technical working group members Number of partners involved will expand over time Although focused on yellow fever, there is potentially scope for collaboration to address general challenges, including: • International and domestic sample transportation

• Laboratory quality assurance 21 Questions?