7200AA21RFA00005 NOFO DEEP VZN signed.pdf

{Insert Funding Opportunity} {Name of Project}

Issue Date: May 13, 2021 Deadline for Questions: May 20, 2021; 1:00 p.m., Washington, DC Time Closing Date: June 17, 2021 Closing Time: 1:00 p.m., Washington, DC Time

Subject: Notice of Funding Opportunity (NOFO) Number: 7200AA21RFA00005

Program Title: Discovery & Exploration of Emerging Pathogens – Viral Zoonoses

(DEEP VZN)

Catalog of Federal Domestic Assistance (CFDA) Number: 98.001

Ladies/Gentlemen:

The United States Agency for International Development (USAID) is seeking applications for a cooperative agreement from qualified entities to implement the Discovery & Exploration of Emerging Pathogens – Viral Zoonoses (DEEP VZN) program. Eligibility for this award is not restricted.

USAID intends to make an award to the applicant(s) who best meets the objectives of this funding opportunity based on the merit review criteria described in this NOFO subject to a risk assessment. Eligible parties interested in submitting an application are encouraged to read this NOFO thoroughly to understand the type of program sought, application submission requirements and selection process.

To be eligible for award, the applicant must provide all information as required in this NOFO and meet eligibility standards in Section C of this NOFO. This funding opportunity is posted on www.grants.gov, and may be amended. It is the responsibility of the applicant to regularly check the website to ensure they have the latest information pertaining to this notice of funding opportunity and to ensure that the NOFO has been received from the internet in its entirety.

USAID bears no responsibility for data errors resulting from transmission or conversion process.

If you have difficulty registering on www.grants.gov or accessing the NOFO, please contact the Grants.gov Helpdesk at 1-800-518-4726 or via email at support@grants.gov for technical assistance.

USAID may not award to an applicant unless the applicant has complied with all applicable unique entity identifier and System for Award Management (SAM) requirements detailed in Section D.6.g. The registration process may take many weeks to complete. Therefore, applicants are encouraged to begin registration early in the process.

Please send any questions to the point(s) of contact identified in Section D. The deadline for questions is shown above. Responses to questions received prior to the deadline will be http://www.grants.gov/ mailto:support@grants.gov furnished to all potential applicants through an amendment to this notice posted to www.grants.gov.

Issuance of this notice of funding opportunity does not constitute an award commitment on the part of the Government nor does it commit the Government to pay for any costs incurred in preparation or submission of comments/suggestions or an application. Applications are submitted at the risk of the applicant. All preparation and submission costs are at the applicant’s expense.

Thank you for your interest in USAID programs.

Sincerely, Patricia Bradley Agreement Officer

TABLE OF CONTENTS

TABLE OF CONTENTS 3

SECTION A: PROGRAM DESCRIPTION 4

SECTION B: FEDERAL AWARD INFORMATION 36

SECTION C: ELIGIBILITY INFORMATION 39

SECTION D: APPLICATION AND SUBMISSION INFORMATION 41

SECTION E: APPLICATION REVIEW INFORMATION 62

SECTION F: FEDERAL AWARD ADMINISTRATION INFORMATION 65

SECTION G: FEDERAL AWARDING AGENCY CONTACT(S) 70

SECTION H: OTHER INFORMATION 71

ANNEX 1 - STANDARD PROVISIONS 72

ANNEX 2 - ABBREVIATIONS AND ACRONYMS 75

ANNEX 3 - PAST PERFORMANCE INFORMATION 76

ANNEX 4 - INITIAL ENVIRONMENTAL EXAMINATION 77

SECTION A: PROGRAM DESCRIPTION

This funding opportunity is authorized under the Foreign Assistance Act (FAA) of 1961, as amended. The resulting award will be subject to 2 CFR 200 – Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards, and USAID’s supplement, 2 CFR 700, as well as the additional requirements found in Section F.

DISCOVERY & EXPLORATION OF EMERGING PATHOGENS – VIRAL ZOONOSES (DEEP VZN)

1. Introduction

The emergence of numerous novel zoonotic viruses [1] over the past few decades is a vivid reminder that countries and the global community remain vulnerable to outbreaks caused by diseases for which there are no specific diagnostics, medicines, or vaccines and for which there is no pre-existing immunity in human populations. Many of these diseases are caused by previously unknown viruses that originated in wild animals before spreading to people directly or through livestock. The health and economic impact associated with these events can be significant [2].

Detection and characterization of unknown zoonotic (i.e. animal-origin) viruses before they cause outbreaks, epidemics, or pandemics in human populations enables more efficient and effective preparedness, prevention, and response efforts, saving lives and limiting economic damage. COVID-19’s severe impacts (more than 140 million cases and 3.0 million deaths along with major economic disruptions spread over 220 countries and territories in Africa, Asia/Pacific, the Americas, Europe, and the Middle East [3]) demonstrate the perils of not having advance information on possible public health threats that can be used to develop tools to inform monitoring and response. The rapid and extensive spread of the COVID-19 pandemic is also a reminder that a threat anywhere can be a threat everywhere.

USAID has invested more than $1.1 billion in global health security since 2005. An extensive area of work between 2009 and 2020 has been viral discovery and characterization in locations where there is high risk for spillover, amplification, and spread of emerging zoonotic viruses [4].

USAID’s on-going multi-sectoral Global Health Security program and its partnerships place the Agency in a unique position to advance efforts related to discovery and characterization of unknown viruses.

Through the new DEEP VZN project, the U.S. Agency for International Development (USAID) seeks to assist a limited number of countries, with a focus on Africa, Asia, and Latin America, to establish capacity to detect, characterize, and disseminate information and findings regarding previously unknown viruses that have originated in wildlife [5]. DEEP VZN will build on more than 15 years of USAID investments in promoting a multisectoral [6] (i.e., “One Health”) approach to addressing emerging zoonotic viruses before they pose an overwhelming epidemic or pandemic threat. Specifically, DEEP VZN will assist targeted African, Asian, and Latin American countries in strengthening their capacities to detect and characterize unknown viruses along chains of transmission where risk profiles favor spillover, amplification, or spread of emerging zoonotic viruses of wildlife origin. Characterization efforts will focus on assessing the zoonotic and pandemic potential of these viruses so that they can be prioritized by other partners for development of tools and countermeasures. The DEEP VZN activities will generate information that can be used by other partners to appropriately address gender in the development of tools and strategies and in the recommendations for any evidence-based viral zoonoses risk mitigation.

2. Overview of USAID’s Global Health Security Program

In partnership with other nations, international organizations, and public and private stakeholders, the U.S. government’s (USG) Global Health Security (GHS) programming aims to prevent avoidable epidemics, detect threats early, and respond rapidly and effectively to disease outbreaks. In May 2019, the Global Health Security Strategy (GHSS) [7] was approved, outlining the USG’s approach to strengthening global health security, including accelerating the capabilities of targeted countries to prevent, detect, and respond to infectious disease outbreaks.

The Strategy pursues three interrelated goals: 1) strengthened partner country global health security capacities; 2) increased international support for global health security; and 3) a homeland prepared and resilient against global health threats. Given its foreign affairs mandate, USAID directly contributes to the first two goals. USAID funds and programs focus on:

addressing the health security capacity gaps in targeted countries at high risk of infectious disease threats and outbreaks (USAID’s major contribution to the Global Health Security Agenda [GHSA]); targeted, applied GHS research; and critical policy and advocacy support for GHS. DEEP VZN will focus on identifying and characterizing novel viral threats which together are critical data needed to address the alarming increase in the frequency and severity of infectious disease outbreaks occurring globally.

3. Evolution of USAID’s Global Health Security Investments

For more than 15 years, USAID has been a leader in the global response to the dangers posed by emerging pandemic threats and has invested in GHS activities with the dual goals of minimizing the impact of existing pandemic influenza threats and pre-empting the emergence and spread of novel epidemic/pandemic threats arising from animal populations. The first phase of the USAID’s GHS program primarily focused on supporting countries to address these zoonotic threats and understanding overall risk of spillover, amplification, and spread in animal and human populations. The One Health approach for achieving these goals was built around a suite of investments and targeted partnerships designed to give earlier insight into the emergence of new public health threats and enhance country-level capacities across sectors to mitigate their potential impact. With a total investment of over $1.1 billion covering countries in Africa, Asia, Latin America, and the Middle East, USAID’s GHS program is the largest and most-extensive One Health program ever implemented. The guiding principles for USAID’s GHS program (2009-2020) have been to:

● build on the understanding that the future well-being of humans, animals, and the environment are inextricably linked, a concept known as “One Health”;

● promote a cross-sectoral, gender-responsive One Health approach that spans the animal health, public health, environmental, and biodiversity/conservation communities;

● support countries to conduct studies to understand risk of spillover, amplification, and spread of known and unknown emerging zoonotic viruses;

● target promotion of policies and strengthening of skills and capacities critical for both minimizing the risk of new disease emergence and the ability to limit their social, economic, and public health impact; and

● use a risk-based approach to target investments where the likelihood of disease emergence is greatest.

Emerging Pandemic Threats-1 (2009-2014): The first iteration of EPT built off of a previous One Health line of work supported by USAID between 2005 and 2009 which was aimed at addressing the immediate threat posed by highly pathogenic H5N1 avian influenza (AI). The EPT-1 portfolio was focused on building the capacities and evidence base needed to mitigate the impact of novel “high-consequence pathogens” arising from animals. Specifically, the EPT-1 portfolio consisted of four complementary activities, including strategic partnerships with the Food and Agricultural Organization of the United Nations (FAO), World Health Organization (WHO) and World Organization for Animal Health (OIE), and was implemented in more than 20 countries across Africa, Asia, and Latin America:

● PREDICT-1: Focused on building a global early warning system for the emergence of diseases that move between wildlife and people, primarily through detection and discovery of viruses from 28 high-consequence viral families in wildlife species that have frequent contact with humans.

● PREVENT: Aimed at characterizing risks associated with practices and behaviors that facilitate disease transmission between animals and humans and developing strategies for lowering the risk of disease spillover.

● IDENTIFY: A partnership among WHO, FAO, and OIE, focused on strengthening laboratory capacities to safely diagnose and report priority animal and human pathogens.

● RESPOND: Focused on the central role of local universities to train cadres of upcoming professionals and practitioners responsible for supporting, promoting, and implementing the One Health approach.

Key accomplishments:

● Established the “proof of principle” that countries can carry out safe capture and sampling of wildlife followed by conventional PCR testing of blood, urine, feces, or oral/nasal swabs for up to 28 families of zoonotic viruses; sampled more than 56,000 animals and identified 815 novel viruses and 169 known viruses, making it the most comprehensive viral detection and discovery effort at that time; identified which animal species (i.e. rodent, bats, and non-human primates) were most associated with spillover of emerging zoonotic viruses; developed a global “hot spots” map for emergence of viral zoonoses. PREDICT-1 final report:

https://ohi.sf.ucdavis.edu/sites/g/files/dgvnsk5251/files/files/page/predict-final-report-lo.pdf.

● Identified that new zoonotic viruses that are capable of infecting diverse host species have higher pandemic potential since these viruses are more likely to amplify by human-to-human transmission with spread on a global scale.

https://www.nature.com/articles/srep14830

● Created region-specific lists of high-risk, human and animal diseases, developed/updated standard lab procedures for these diseases, and provided viral identification training for https://ohi.sf.ucdavis.edu/sites/g/files/dgvnsk5251/files/files/page/predict-final-report-lo.pdf https://ohi.sf.ucdavis.edu/sites/g/files/dgvnsk5251/files/files/page/predict-final-report-lo.pdf https://www.nature.com/articles/srep14830 laboratories in Africa and Asia.

https://www.usaid.gov/sites/default/files/documents/1864/IDENTIFY-Compilation-of- Accomplishments__1 -13-2014.docx

● Characterized the nature and frequency of human contact with animals in Africa and Asia. https://www.fhi360.org/projects/prevent-%E2%80%94-emerging-pandemic-threats

● Improved the effectiveness of poultry vaccination in Indonesia (with demonstrated decrease in reported poultry outbreaks and human infections) by identifying which licensed vaccines were efficacious against the specific H5N1 avian influenza virus present in the country.

https://ec.europa.eu/food/sites/food/files/animals/docs/ad_cm_ai_nrl-annual-meetings- 14_pres-17.pdf

● Established two regional university networks (Central/East Africa and Southeast Asia) and four country university networks (Indonesia, Malaysia, Thailand, Vietnam) to formulate and introduce standardized One Health curricula for pre- and in-service training and serve as a One Health hub across participating universities and countries.

Lessons learned:

● The understanding of risk associated with spillover of emerging zoonotic viruses from animals to people could be further improved by focusing on a smaller subset of viral families and animal species (to allow for larger sample sizes for viral detection), adding surveillance of humans (virology and serology), focusing on common points where animals and humans interact (with behavioral surveillance), and sampling longitudinally in order to gain insight on any seasonality associated with spillover of emerging zoonotic viruses from animals to people.

● Universities play a critical role in creating long-term changes to workforce skills. They work on the cutting edge of their fields to educate students who will comprise tomorrow’s workforce. Universities are also testing sites for education, where innovative and trans-disciplinary approaches to training professionals are constantly introduced and refined, including One Health approaches. By investing in universities in developing countries, we can create a long-term in-country capability for improved human resource capacity.

● Focused public sector investments in filling key knowledge gaps related to spillover, amplification, and spread of emerging zoonotic viruses can lead to private sector poultry producers changing their practices (if cost-neutral) based on evidence, thereby increasing the likelihood of sustainability.

● Behavior change communications for AI that were targeted at households increased knowledge, but did not change behaviors possibly because doing so cost more (e.g.

buying fencing for household birds, buying feed for caged birds that were previously free-ranging) and/or because the risk of human infection was perceived to be much lower than other common diseases such as malaria or tuberculosis.

● Countries which did not have a strong history of cross-sectoral collaboration on zoonotic diseases, especially those in Africa, would benefit from support to establish or strengthen in-country platforms to coordinate zoonotic disease activities across sectors, especially public health, livestock, and wildlife.

EPT-2 (2014-2020): The second iteration of EPT built on the investments, partnerships, and lessons learned from EPT-1. The focus remained on preventing, detecting, and responding to https://www.usaid.gov/sites/default/files/documents/1864/IDENTIFY-Compilation-of-Accomplishments__1%20-13-2014.docx https://www.usaid.gov/sites/default/files/documents/1864/IDENTIFY-Compilation-of-Accomplishments__1%20-13-2014.docx https://www.fhi360.org/projects/prevent-%E2%80%94-emerging-pandemic-threats https://ec.europa.eu/food/sites/food/files/animals/docs/ad_cm_ai_nrl-annual-meetings-14_pres-17.pdf https://ec.europa.eu/food/sites/food/files/animals/docs/ad_cm_ai_nrl-annual-meetings-14_pres-17.pdf emerging viral diseases using a One Health approach, but broadened investments around preparedness. The scope of the program also was expanded to address the threats posed by antimicrobial resistance (AMR), as the inappropriate use of antibiotics in animal husbandry and inappropriate “prescriber-user” practices associated with antibiotic use in clinical care were increasingly understood to be core drivers behind the emergence and global spread of antibiotic-resistant organisms. EPT-2 worked in more than 30 countries across Africa [8], Asia, and the Middle East [9], and was comprised of three activities as well as partnerships with FAO and

WHO:

● PREDICT-2: Consolidated the scopes of EPT-1’s PREDICT-1 and PREVENT to more-precisely identify and characterize emerging zoonotic viruses in animals and people, as well as behaviors, practices, and conditions associated with viral evolution, spillover, amplification, and spread. The number of targeted viral families was reduced to four [10] and targeted animal-human interfaces reduced to households, markets, and livestock/agricultural production. Longitudinal monitoring at high risk interfaces, human surveillance, animal and human serology, and foci on Ebola in West Africa, Middle East Respiratory Syndrome coronavirus (MERS-CoV) in northeast Africa, and SARS-CoV-2 in Asia were also added.

● Preparedness and Response (P&R): Assisted countries in establishing and strengthening national One Health platforms to develop, formalize, and maintain multisectoral collaboration as well as develop country-specific plans for responding to public health events of unknown etiology.

● One Health Workforce (OHW): Built on the investments of EPT-1’s RESPOND by strengthening the capacity of the One Health university networks to address the current workforce needs of ministries in addition to building a pipeline of future One Health workers, expanding the networks to include more countries, and strengthening the operational capacities of the university networks.

● FAO: Focused on risk characterization activities to understand biological drivers of zoonotic virus spillover (including AI and MERS-CoV), amplification, and spread;

studied and promoted risk mitigation policies and practices for livestock that reduce the risk of zoonotic virus spillover, amplification, and spread; supported national One Health platforms (in coordination with P&R); strengthened national preparedness within the livestock sector to respond to events of public health concern including epidemiology training for veterinarians; strengthened global livestock surveillance networks; and provided emergency lab, commodity, and other support for outbreaks in livestock.

● WHO: Focused on strengthening influenza surveillance; strengthening national preparedness within the public health sector to respond to events of public health significance; supported One Health national platforms through the development of tools (in coordination with P&R) and invested in a One Health workforce (in coordination with OHW); and provided emergency lab, commodity, and other support for outbreaks in humans.

Key accomplishments:

● Conducted standardized and synchronized monitoring of wildlife, humans, and associated behaviors at specific animal-human interfaces across 28 countries; sampled >100,000 animals and humans and identified an additional 200 novel viruses (including a new Ebola species in Sierra Leone and Guinea and a new coronavirus associated with swine deaths in China) and 88 known viruses (in addition to those detected under PREDICT-1);

and identified an association between RNA virus shedding by wildlife and animal value chains.

PREDICT final report:

https://ohi.vetmed.ucdavis.edu/sites/g/files/dgvnsk5251/files/inline-files/PREDICT%20LEGACY%20-%20FINAL%20FOR%20WEB_0.pdf

PREDICT data:

http://data.predict.global/, https://data.usaid.gov/Global-Health-Security-in- Development-GHSD-/PREDICT-Emerging-Pandemic-Threats-Project- Restrict/cn2r-e2df https://data.usaid.gov/Global-Health-Security-in-Development-GHSD- /PREDICT-Emerging-Pandemic-Threats-Project/tqea-hwmr

Other PREDICT information:

https://www.nature.com/articles/s41564-018-0227-2 https://www.nature.com/articles/s41586-018-0010-9 , https://www.sciencemag.org/news/2019/01/bat-species-may-be-source-ebola-epidemic-killed-more-11000-people-west-africa, https://ohi.vetmed.ucdavis.edu/programs-projects/predict-project/reports , https://static1.squarespace.com/static/5c7d60a711f7845f734d4a73/t/5e95fb72530 9184f8a1e76b2/15868875%2090640/PREDICT+March+18+Data+Discussion.pd f , https://p2.predict.global/interventions , https://p2.predict.global/insights , https://ohi.vetmed.ucdavis.edu/programs-projects/predict-proect/publications

● Developed and made publicly-available a tool for ranking the risk of animal-to-human spillover for newly discovered viruses originating in wildlife.

https://www.pnas.org/content/pnas/118/15/e2002324118.full.pdf

● With CDC, co-identified Marburg virus in Sierra Leone, the first-ever detection of the virus in West Africa. https://www.ucdavis.edu/health/news/deadly-marburg-virus-found-sierra-leone-bats/, https://www.nature.com/articles/s41467-020-14327-8

● Collected evidence indicating previously-unrecognized spillover of Ebola viruses in the Democratic Republic of the Congo and Uganda and provided evidence that Ebola/Bombali is zoonotic.

https://academic.oup.com/jid/article/218/suppl_5/S277/5039952;

https://link.springer.com/epdf/10.1186/s42522-020-00028- 1?sharing_token=J6AZyoFlW_WXSCHlhrCB2m_BpE1tBhCbnbw3BuzI2RMvLJRJHN UVHei-FofO0OKe-pIHezGL0eAuEIr6l4pqvwl2HiTJ1uK7ENb4miIpp90R0pBn4tk8Jkh1T3HM1jnl0Qny1-ns6xNrk5LC44OB-iT3a6VVSHNO4DKeZxY8N7A%3D

● Identified a SARS-like coronavirus from bats in China that had spilled over to people https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178078/

● To overcome low positivity rates for filoviruses among healthy animals, a strategy was developed and deployed in Guinea, Liberia, and Sierra Leone to generate large numbers of samples among the most-likely animal hosts (based on evidence from previous studies) and viral detection was intentionally conducted for filoviruses rather than narrowly for https://ohi.vetmed.ucdavis.edu/sites/g/files/dgvnsk5251/files/inline-files/PREDICT%20LEGACY%20-%20FINAL%20FOR%20WEB_0.pdf https://ohi.vetmed.ucdavis.edu/sites/g/files/dgvnsk5251/files/inline-files/PREDICT%20LEGACY%20-%20FINAL%20FOR%20WEB_0.pdf http://data.predict.global/ http://data.predict.global/ https://data.usaid.gov/Global-Health-Security-in-Development-GHSD-/PREDICT-Emerging-Pandemic-Threats-Project-Restrict/cn2r-e2df https://data.usaid.gov/Global-Health-Security-in-Development-GHSD-/PREDICT-Emerging-Pandemic-Threats-Project-Restrict/cn2r-e2df https://data.usaid.gov/Global-Health-Security-in-Development-GHSD-/PREDICT-Emerging-Pandemic-Threats-Project-Restrict/cn2r-e2df https://data.usaid.gov/Global-Health-Security-in-Development-GHSD-/PREDICT-Emerging-Pandemic-Threats-Project/tqea-hwmr https://data.usaid.gov/Global-Health-Security-in-Development-GHSD-/PREDICT-Emerging-Pandemic-Threats-Project/tqea-hwmr https://www.nature.com/articles/s41564-018-0227-2 https://www.nature.com/articles/s41586-018-0010-9 https://www.sciencemag.org/news/2019/01/bat-species-may-be-source-ebola-epidemic-killed-more-11000-people-west-africa https://www.sciencemag.org/news/2019/01/bat-species-may-be-source-ebola-epidemic-killed-more-11000-people-west-africa https://ohi.vetmed.ucdavis.edu/programs-projects/predict-project/reports https://static1.squarespace.com/static/5c7d60a711f7845f734d4a73/t/5e95fb725309184f8a1e76b2/15868875%2090640/PREDICT+March+18+Data+Discussion.pdf https://static1.squarespace.com/static/5c7d60a711f7845f734d4a73/t/5e95fb725309184f8a1e76b2/15868875%2090640/PREDICT+March+18+Data+Discussion.pdf https://static1.squarespace.com/static/5c7d60a711f7845f734d4a73/t/5e95fb725309184f8a1e76b2/15868875%2090640/PREDICT+March+18+Data+Discussion.pdf https://p2.predict.global/interventions https://p2.predict.global/insights https://ohi.vetmed.ucdavis.edu/programs-projects/predict-proect/publications https://www.pnas.org/content/pnas/118/15/e2002324118.full.pdf https://www.ucdavis.edu/health/news/deadly-marburg-virus-found-sierra-leone-bats/ https://www.ucdavis.edu/health/news/deadly-marburg-virus-found-sierra-leone-bats/ https://www.nature.com/articles/s41467-020-14327-8 https://academic.oup.com/jid/article/218/suppl_5/S277/5039952 https://link.springer.com/epdf/10.1186/s42522-020-00028-1?sharing_token=J6AZyoFlW_WXSCHlhrCB2m_BpE1tBhCbnbw3BuzI2RMvLJRJHNUVHei-FofO0OKe-pIHezGL0eAuEIr6l4pqvwl2HiTJ1uK7ENb4miIpp90R0pBn4tk8Jkh1T3HM1jnl0Qny1-ns6xNrk5LC44OB-iT3a6VVSHNO4DKeZxY8N7A%3D https://link.springer.com/epdf/10.1186/s42522-020-00028-1?sharing_token=J6AZyoFlW_WXSCHlhrCB2m_BpE1tBhCbnbw3BuzI2RMvLJRJHNUVHei-FofO0OKe-pIHezGL0eAuEIr6l4pqvwl2HiTJ1uK7ENb4miIpp90R0pBn4tk8Jkh1T3HM1jnl0Qny1-ns6xNrk5LC44OB-iT3a6VVSHNO4DKeZxY8N7A%3D https://link.springer.com/epdf/10.1186/s42522-020-00028-1?sharing_token=J6AZyoFlW_WXSCHlhrCB2m_BpE1tBhCbnbw3BuzI2RMvLJRJHNUVHei-FofO0OKe-pIHezGL0eAuEIr6l4pqvwl2HiTJ1uK7ENb4miIpp90R0pBn4tk8Jkh1T3HM1jnl0Qny1-ns6xNrk5LC44OB-iT3a6VVSHNO4DKeZxY8N7A%3D https://link.springer.com/epdf/10.1186/s42522-020-00028-1?sharing_token=J6AZyoFlW_WXSCHlhrCB2m_BpE1tBhCbnbw3BuzI2RMvLJRJHNUVHei-FofO0OKe-pIHezGL0eAuEIr6l4pqvwl2HiTJ1uK7ENb4miIpp90R0pBn4tk8Jkh1T3HM1jnl0Qny1-ns6xNrk5LC44OB-iT3a6VVSHNO4DKeZxY8N7A%3D https://link.springer.com/epdf/10.1186/s42522-020-00028-1?sharing_token=J6AZyoFlW_WXSCHlhrCB2m_BpE1tBhCbnbw3BuzI2RMvLJRJHNUVHei-FofO0OKe-pIHezGL0eAuEIr6l4pqvwl2HiTJ1uK7ENb4miIpp90R0pBn4tk8Jkh1T3HM1jnl0Qny1-ns6xNrk5LC44OB-iT3a6VVSHNO4DKeZxY8N7A%3D https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178078/

Ebola/Zaire which was the cause the 2014-2016 human epidemic in West Africa. (See chapter on Ebola Host Project in PREDICT final report.)

● Used PCR and serology to screen animal and human samples from Asia collected under PREDICT (from 2009-2020) for evidence of active or previous infections with SARS- CoV-2 and/or related coronaviruses. Preliminary virological results include detection of two novel SARS-related coronaviruses in specimens from nine animals and non-SARS-related coronaviruses (including two novel viruses) in specimens from 72 additional animals. From 3,329 individuals tested, antibodies to SARS-related coronaviruses were detected in 35 people and antibodies to other non-SARS-related coronaviruses were detected in three people. See https://www.nature.com/articles/s41467-021-21240-1 and https://www.biorxiv.org/content/10.1101/2021.01.26.428212v1.full.pdf.

● Studies from northeast Africa have documented high exposure rates of camels to MERS- CoV viruses with most of the viruses sequenced to date clustering in clade C. This group is distinct from the one that contains the known zoonotic MERS-CoV viruses from the Arabian Peninsula, but there is some experimental evidence by other researchers that some clade C viruses may be zoonotic as well despite the absence of documented human infections in northeast Africa.

https://www.liebertpub.com/doi/10.1089/vbz.2016.2062?url_ver=Z39.88- 2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&= https://www.tandfonline.com/doi/full/10.1080/22221751.2018.1560235, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258726/, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2017.22.11.30487, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723520/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605751/

● Developed and validated a rapid, easy-to-use field diagnostic for identifying H5 and H7 influenza A viruses in birds which allows for faster response to contain these viruses in infected flocks and prevent spread to additional animals or people.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/irv.12646.

● Developed “Living Safely with Bats” and “Living Safely with Animals” communication tools to convey risk and possible risk-reduction options to communities in West and East African countries. [Note: these two tools have not yet been evaluated for effectiveness in increasing knowledge or changing behaviors.] https://p2.predict.global/living-safely-with-bats-book, https://documentcloud.adobe.com/link/track?uri=urn%3Aaaid%3Ascds%3AUS%3A595 7e613-ecba-4dd4-bc7e-1fa4d60c786b#pageNum=22

● With the Australian Department of Foreign Affairs and Trade and FAO, enhanced farm and market biosecurity, flock health and hatchery management practices contributing to reduced disease and AMR risk in Cambodia, Laos, Myanmar, and Vietnam.

http://www.fao.org/3/ca5608en/CA5608EN.pdf http://www.fao.org/3/ca5515en/ca5515en.pdf http://www.fao.org/3/ca5516en/ca5516en.pdf http://www.fao.org/3/ca6642en/CA6642EN.pdf http://www.fao.org/3/ca7319en/CA7319EN.pdf http://www.fao.org/3/ca6114en/CA6114EN.pdf https://www.nature.com/articles/s41467-021-21240-1 https://www.biorxiv.org/content/10.1101/2021.01.26.428212v1.full.pdf https://www.liebertpub.com/doi/10.1089/vbz.2016.2062?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&=& https://www.liebertpub.com/doi/10.1089/vbz.2016.2062?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&=& https://www.liebertpub.com/doi/10.1089/vbz.2016.2062?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&=& https://www.tandfonline.com/doi/full/10.1080/22221751.2018.1560235 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258726/ https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2017.22.11.30487 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723520/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605751/ https://onlinelibrary.wiley.com/doi/pdf/10.1111/irv.12646 https://p2.predict.global/living-safely-with-bats-book https://documentcloud.adobe.com/link/track?uri=urn%3Aaaid%3Ascds%3AUS%3A5957e613-ecba-4dd4-bc7e-1fa4d60c786b#pageNum=22 https://documentcloud.adobe.com/link/track?uri=urn%3Aaaid%3Ascds%3AUS%3A5957e613-ecba-4dd4-bc7e-1fa4d60c786b#pageNum=22 http://www.fao.org/3/ca5608en/CA5608EN.pdf http://www.fao.org/3/ca5515en/ca5515en.pdf http://www.fao.org/3/ca5516en/ca5516en.pdf http://www.fao.org/3/ca6642en/CA6642EN.pdf http://www.fao.org/3/ca7319en/CA7319EN.pdf http://www.fao.org/3/ca6114en/CA6114EN.pdf

● Refined the global “hot spots” analyses for emergence of viral zoonoses.

https://www.ecohealthalliance.org/wp-content/uploads/2017/10/s41467-017-00923-8.pdf.

● Further refined the understanding of Nipah virus dynamics in bats and implications for spillover to humans. https://www.pnas.org/content/early/2020/10/27/2000429117

● Developed tools, lessons learned, and economic analyses related to One Health programming and provided technical assistance and operational support to 15 One Health platforms in Africa and Asia.

● Developed and implemented a district-level, in-service applied veterinary epidemiology training program (ISAVET) in East, Central, and West African countries to address the dearth of veterinarians with agricultural- and veterinary-specific epidemiologic core competencies. http://www.fao.org/resilience/news-events/detail/en/c/1171750/

● Provided classroom and hands-on training in One Health core competencies to over 13,300 undergraduate students and 33,500 current One Health professionals across Africa and Asia.

● Developed gender-responsive curriculum and training of One Health professionals:

Gender One Health and Infectious Disease Training Module.

http://afrohun.org/index.php?option=com_content&view=article&id=168&Itemid=1055

● Supported prevention, detection, and response to infectious disease threats through the Global Health Security Agenda. https://www.state.gov/wp-content/uploads/2020/09/GHSA_ProgressImpactFY19_final.pdf

Lessons learned:

● Concurrent, focused, and longitudinal surveillance of wildlife and human populations have provided additional insight on where, when, and how emerging zoonotic viruses (including Ebola) spill over at specific animal-human interfaces; this insight is critical to strengthening the ability of countries to begin developing and testing the effectiveness of interventions to reduce the risk of spillover of these threats from animals to people (although additional information related to spillover risk is needed for viruses such as Ebola, Nipah, animal-origin coronaviruses, and animal-origin influenzas).

● Characterization of novel viruses for zoonotic and pandemic potential remains a lengthy and expensive process which often relies on sharing samples and specialized capacities across multiple countries. Efforts to streamline and consistently support characterization are needed in order to identify which novel viruses are likely to be high-consequence (i.e.

zoonotic and epidemic/pandemic potential) before they cause outbreaks.

● In Africa and Asia, the continued spillover, amplification, and spread of emerging zoonotic viruses highlight the large gaps that still exist in biosafety and biosecurity, particularly along animal value chains; the private sector so far has been an underutilized partner for broadly (as opposed to addressing disease by disease) reducing risk along livestock value chains. Reducing the risk of spillover of zoonotic viruses from wildlife to livestock and people (including through animal value chains) is also a gap that needs to be addressed.

● Workforce transformation is a long-term process that requires consultation and collaboration with a diverse set of stakeholders and a better understanding of labor markets’ supply and demand curves. In order to better understand and target training opportunities and educational offerings, One Health university networks (OHUNs) must https://www.ecohealthalliance.org/wp-content/uploads/2017/10/s41467-017-00923-8.pdf https://www.pnas.org/content/early/2020/10/27/2000429117 http://www.fao.org/resilience/news-events/detail/en/c/1171750/ http://afrohun.org/index.php?option=com_content&view=article&id=168&Itemid=1055 https://www.state.gov/wp-content/uploads/2020/09/GHSA_ProgressImpactFY19_final.pdf https://www.state.gov/wp-content/uploads/2020/09/GHSA_ProgressImpactFY19_final.pdf consult and collaborate with governments, non-governmental organizations (NGOs), donors, and the private sector on their needs and capacities.

● While countries appear to understand the benefits of One Health platforms and have utilized new tools developed with support from EPT-2, the degree to which countries engage with and support their platforms varies, and this has implications for long-term sustainability and the ability to attract donor funding.

GHSA: In 2014, USAID, along with other USG partners, including the National Security Council, Department of State, the U.S. Centers for Disease Control and Prevention (CDC), and the Department of Defense, joined more than 60 countries in implementing the GHSA. At the core of the GHSA is the goal of strengthening capacities for prevention, detection, and response for infectious disease outbreaks using multisectoral collaboration across public health, medicine, agriculture, animal/veterinary health, environment, education/academia, and defense/security agencies. USAID’s GHSA activities have been geographically focused in 16 countries in Africa and Asia and used to build workforce capacity and surveillance, laboratory capacity, and preparedness and response systems for addressing prioritized endemic and emerging zoonotic threats. Going forward, USAID’s emerging threats and GHSA activities constitute the agency’s global health security investments under the GHSS. Countries supported by USAID under EPT-1 and EPT-2/GHSA are shown in the map below. Between 2020 and 2025, USAID will continue its global health security investments with a primary focus on countries in Africa and Asia, although countries in Latin America may be included for viral discovery. DEEP VZN will complement other USAID partnerships that are described below in section 5 (“Collaboration with Other USAID/External Partners”).

4. DEEP VZN Goal & Objectives

Problem Statement

An analysis of 335 emerging infectious diseases (EID) in humans between 1940 and 2004 revealed a number of important characteristics including: the incidence of EID events is increasing over time; 60% of EIDs are zoonotic and, of those, 72% are from wildlife; the origins of EIDs are correlated with socio-economic, environmental, and ecological factors and are concentrated in tropical and subtropical regions of the world; and global resources to address EIDs are poorly allocated [11]. Zoonotic diseases cause the loss of lives and livelihoods by disrupting local, regional, and global travel and trade, and by threatening the economic and political stability of some of the most vulnerable countries. Among zoonotic diseases, emerging zoonotic viruses are particularly problematic because: these pathogens generally lack specific treatments and vaccines (for animals or people); human populations are more likely to be immunologically naive to novel viral zoonoses giving these pathogens a comparatively-higher likelihood of epidemic/pandemic potential; and these pathogens are often detected during or after amplification or spread in human populations which challenges containment. The on-going COVID-19 pandemic caused by SARS-CoV-2–with more than 3.2 million deaths and an estimated economic loss of at least $28 trillion [12]—has once again highlighted the importance of these three points as well as the significant time lag associated with developing and deploying diagnostics, medicines, vaccines, and risk-reduction interventions after a new zoonotic virus has emerged.

Multiple, previously-unknown zoonotic viruses have emerged and caused outbreaks over the past three decades. Many of these viruses originated in wild animals before spreading to people directly or through livestock such as poultry, swine, horses, and camels. A recent study estimated that there may be an additional 1.67 million undiscovered viruses in mammals and birds, with between 631,000 and 827,000 capable of infecting people [13]. Countries and the international community would be better served, in terms of lives saved and economic damage limited, if they were able to detect and assess the zoonotic and epidemic/pandemic potential of novel zoonotic viruses before they cause widespread outbreaks. However, countries do not routinely invest in monitoring for and characterizing infectious disease threats in advance of their emergence. As a result, the lack of data on new emerging zoonotic viruses is a serious impediment to countries and the international community being able to prevent and prepare for future threats (sometimes also referred to as “Disease X”). This advance work includes both reducing the likelihood of initial viral spillover from animals to people as well as developing or updating diagnostics and medical countermeasures for new emerging zoonotic viruses.

Building on previous USAID global analyses of risk and investments in countries under EPT-1 and EPT-2/GHSA, the Agency is now employing a dual track strategy to prevent and prepare for future emerging zoonotic viruses with epidemic/pandemic potential (see figure below). Track one aims to refine and employ interventions to address the on-going spillover, amplification, and spread of known emerging zoonotic viruses through a recently-awarded project, STOP Spillover. This project will assist countries to: understand the factors that contribute to the risk of spillover of pathogens from wildlife to humans; develop, assess, and implement early risk-reduction interventions that will reduce the spillover and spread of these threats; and recognize and respond rapidly to zoonotic spillover events [14].

Track two of USAID’s strategy for addressing emerging zoonotic viruses includes the new DEEP VZN project, which will specifically focus on supporting a multi-country project to detect unknown viruses and characterize their zoonotic and epidemic/pandemic potential and share this information with the greater scientific/One Health community. USAID’s support for viral discovery since 2009 and its multi-sectoral GHS Program and partnerships place the Agency in a unique position to meaningfully advance these lines of work.

DEEP VZN Goal: Through in-country institutions, detect and characterize unknown viruses with zoonotic and epidemic/pandemic potential along high-risk chains of transmission to provide data which is publicly shared so that other partners can use them for risk mitigation, policy reform, and development of diagnostics, medicines, and vaccines.

USAID’s expectation is that the successful applicant will support host-country institutions and staff in identifying sampling locations (based on risk along chains of transmission), detecting and characterizing unknown viruses, and actively sharing data and analyses with in-country and global stakeholders.

Estimated Budget: total of up to $125 million over five years (2021-2026).

DEEP VZN Strategic Approach: Building upon an institutional legacy in viral zoonoses landscaping and risk analyses, USAID’s DEEP VZN Project seeks to strengthen and expand in-country capacities that will considerably advance the detection and characterization processes for unknown viruses with zoonotic and epidemic/pandemic potential. Applicants are expected to reflect this approach by focusing resources on in-country partnerships and sub-awards. DEEP VZN will build on data, tools, and strategies--including those previously developed by PREDICT and FAO with USAID support as well as those supported by other USG agencies and international partners--to strengthen the capacity of a limited number of in-country institutions that will conduct the sampling, detection, and characterization of unknown viruses.

Lessons learned from viral discovery and characterization efforts to date include:

● Previous work has identified chains of transmission, species, and geographic “hot spots” in Africa, Asia, and Latin America and the Middle East where viral detection rates are higher.

● Detecting known and unknown viral threats can safely be accomplished by in-country laboratories and staff.

● While significant, the scale of viral discovery and characterization to date has been relatively small. Improvements in efficiency of sampling, detection, and characterization hold the potential to dramatically increase the scale of data available on unknown viruses and their emergence risk.

● To date, the global community lacks efficient, low-cost, biosafe/biosecure, and standardized methods to reliably characterize newly-identified viruses to determine their zoonotic and epidemic/pandemic potential.

● Focused public and private investments can fill key knowledge gaps to help individuals, communities, governments, and the private sector to reduce risk. However, there is room for improving the speed and extent to which the research findings (specifically detection and characterization of novel viruses) are available to and taken up by those who assess risk, operate surveillance systems and laboratories, mitigate risk, and develop diagnostics, medicines, and vaccines.

An essential component of DEEP VZN is improving the efficiency of viral detection and characterization in order to identify novel viruses on a much greater scale than previously possible. A key part of this approach will be the use of specific, evidence-based sampling strategies for each country to increase detection rates for unknown viruses in the prioritized families (see below for more information). Such approaches have been successfully employed in China where the geographic distribution of specific host taxa have been important considerations for where to set up sampling in order to detect coronaviruses [15, 16]; in Vietnam where sampling specific interfaces has been shown to impact detection rates for coronaviruses along wildlife value chains [17]; and in East Africa where shedding of coronaviruses by bats occurs at specific times of the year [18].

Through the support provided by DEEP VZN, focus countries will be able to enhance their capacity to detect and assess the zoonotic and epidemic/pandemic potential of previously-unknown viruses. The resulting data will also be used to answer global questions about geographic distribution of novel viruses, which animals can serve as hosts, and nodes along chains of transmission where spillover, amplification, or spread occur. These data potentially can be used by other USAID, USG, and other projects and programs—such as STOP Spillover—to model disease emergence risk, update risk analyses, direct precision surveillance approaches, and implement targeted risk-reduction measures. In addition, information from DEEP VZN could be used by other partners, including donors and the private sector, to develop and pre-position diagnostics, medicines, and vaccines ahead of costly and disruptive epidemics and pandemics.

Because spillover, amplification, and spread of unknown emerging zoonotic viruses potentially affects wildlife, livestock, and human populations, efforts to detect and characterize unknown viral threats under the DEEP VZN project will require in-country (and possibly regional and global) partnerships that are collaborative and multisectoral.

DEEP VZN will focus on the viral characterization process outlined in the figure below. (More information on the four objectives of DEEP VZN is included further below.) The interlinked objectives cover: collecting samples; detecting, characterizing, and prioritizing new viruses detected; and analyzing and sharing the findings in-country and globally. USAID expects that

DEEP VZN will identify/generate samples for viral detection throughout the life of the project and that viral detection and characterization will take place as soon as possible after collection to ensure that information on viral detection and characterization can be rapidly shared with the country and global scientific/One Health community.

DEEP VZN’s Viral Characterization Process

The in-country sampling for unknown viruses under DEEP VZN will serve two very important functions. First, the data generated will be used to identify future infectious disease threats before large outbreaks occur which potentially allows time for other partners to develop or update surveillance postures and risk-reduction measures as well as pre-position diagnostics, medicines, and vaccines (if available). Second, the laboratory techniques for detection of unknown viruses may also be used to assist in the investigation of events of unknown etiology when common pathogens have been ruled out. While some low- and middle-income countries have developed strategies over the past decade to sample for emerging zoonotic viruses, this ability is presently limited in size and scope, not sustainable without external donor funding, and may not be focused along the highest-risk chains of transmission. As a result, these countries have a poorly differentiated understanding of spillover risk, limiting their ability to effectively prevent, detect, and respond to future emergence of viral zoonoses.

Data collection, analysis, storage, and sharing. DEEP VZN is expected to generate actionable data on potential future threats, therefore it is critical that there be a robust data storage and sharing effort so that information on novel viruses will be actively shared with end-users, to include affected communities, policy makers, private sector, and research institutions. Metadata and viral detection and characterization results from DEEP VZN will be stored in-country using existing systems (with augmentation by DEEP VZN, if needed). Since USAID expects that data generated by DEEP VZN will be publicly available—carrying appropriate data utilization rights—through open source platforms for the benefit of global health research and risk analyses, DEEP VZN will assist in linking in-country data with global systems (e.g. GenBank, GISAID) where appropriate. Knowledge gained by DEEP VZN on novel viruses assessed to be zoonotic and significant epidemic/pandemic threats will be immediately available to the in-country owners of the data and will be expected to be available expeditiously to policy makers, the private sector, and implementing partners so that they are able to take steps to improve surveillance and reduce the risk of viral spillover [see reference 19 for examples of partners that could use this information].