Foa_Content_of_RFA-CK-22-001 FORMS F.pdf

Centers for Disease Control and Prevention

National Center for Emerging and Zoonotic Infectious Diseases

Investigation of Monkeypox and Other Zoonotic Diseases in the Democratic Republic of the Congo (DRC)

RFA-CK-22-001

02/28/2022

Table of Contents Section I. Funding Opportunity Description

Section II. Award Information

Section III. Eligibility Information

Section IV. Application and Submission Information

Section V. Application Review Information

Section VI. Award Administration Information

Section VII. Agency Contacts

Section VIII. Other Information

Overview Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Components of Participating Organizations:

National Center for Emerging and Zoonotic Infectious Diseases Notice of Funding Opportunity (NOFO) Title Investigation of Monkeypox and Other Zoonotic Diseases in the Democratic Republic of the Congo (DRC) Activity Code U01 – Research Project - Cooperative Agreement

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-CK-22-001

Assistance Listings Number(s) 93.084 Category of Funding Activity HL - Health NOFO Purpose The purpose of this notice of funding opportunity (NOFO) is to support research to investigate the epidemiological, ecological, and anthropological aspects of monkeypox (MPX) and to assess clinical intervention strategies in the Democratic Republic of Congo (DRC), including one study site in Tshuapa Province. Applications may also propose research extending to other zoonotic and vaccine-preventable diseases that are of importance in the DRC. Research activities should focus on improvement and evaluation of lab-based surveillance systems, investigations of animal reservoirs and human behaviors at the human-animal interface, epidemiologic investigations, genome sequencing and phylogenetic analysis, risk mitigation, enhancing health communication strategies, and clinical evaluation of vaccines and therapeutic treatments. The research supported by this NOFO should provide the DRC Ministry of Health and other key stakeholders with evidence-based strategies to develop interventions.

Key Dates Publication Date:

To receive notification of any changes to RFA-CK-22-001, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link.

An email address is needed for this service.

Letter of Intent Due Date:

The LOI date will generate once the Synopsis is published if Days or a Date are entered.

1/31/2022

Application Due Date:

02/28/2022 02/28/2022

On-time submission requires that electronic applications be error-free and made available to CDC for processing from the NIH eRA system on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov no later than 5:00 PM U.S. Eastern Time.

Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because it provides a validation of all requirements prior to submission and prevents errors.

For more information on accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via http://grants.nih.gov/support/index.html.

E-mail: commons@od.nih.gov Phone: 301-402-7469 or (toll-free) 1-866-504-9552.

Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays.

Note: HHS/CDC grant submission procedures do not provide a grace period beyond the application due date time to correct any error or warning notices of noncompliance with application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review:

04/28/2022 Secondary Review:

06/24/2022 Estimated Start Date:

09/30/2022 Expiration Date:

https://www.grants.gov/ http://grants.nih.gov/support/index.html mailto:commons@od.nih.gov

03/01/2022 Required Application Instructions It is critical that applicants follow the instructions in the How to Apply - Application Guide except where instructed to do otherwise in this NOFO. Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note:The Research Strategy component of the Research Plan is limited to 20 pages.

Page Limitations: Pages that exceed the page limits described in this NOFO will be removed and not forwarded for peer review, potentially affecting an application's score.

Applications that do not comply with these instructions may be delayed or may not be accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary Purpose: The purpose of this notice of funding opportunity (NOFO) is to support research to investigate the epidemiological, ecological, and anthropological aspects of monkeypox (MPX) and to assess clinical intervention strategies in the Democratic Republic of Congo (DRC), including one study site in Tshuapa Province. Applications may also propose research extending to other zoonotic and vaccine-preventable diseases that are of importance in the DRC. Research activities should focus on improvement and evaluation of lab-based surveillance systems, investigations of animal reservoirs and human behaviors at the human-animal interface, epidemiologic investigations, genome sequencing and phylogenetic analysis, risk mitigation, enhancing health communication strategies, and clinical evaluation of vaccines and therapeutic treatments. The research supported by this NOFO should provide the DRC Ministry of Health and other key stakeholders with evidence-based strategies to develop interventions.

Mechanism of Support: U01 - Research Project - Cooperative Agreement Funds Available and Anticipated Number of Awards: The estimated total funding available, including direct and indirect costs, for the entire five (5)-year project period is $3,500,000. The anticipated number of awards is one. Awards issued under this NOFO are contingent upon availability of funds and a sufficiently meritorious application. The total amount awarded will depend upon the quality, duration and cost of the application received.

Budget and Project Period: The estimated total funding (direct and indirect) for the first year (12-month budget period) is $700,000. The estimated total funding (direct and indirect) for the entire project period is $3,500,000. The project period is anticipated to run from 09/30/2022 to 09/29/2027.

Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. “Application and Submission Information” of this announcement.

https://grants.nih.gov/grants/how-to-apply-application-guide.html

Eligible Institutions/Organizations. Institutions/organizations listed in Section III. of this announcement are eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. NOTE: CDC does not make awards to individuals directly. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply.

Number of PDs/PIs. There will only be one PD/PI for each application.

Number of Applications. Only one application per institution (normally identified by having a unique DUNS number) is allowed.

Application Type. New Application Materials. See Section IV.1 for application materials. Please note that

SF424 (R&R) FORMS-F is to be used when completing the application package. Please see https://grants.nih.gov/grants/how-to-apply-application-guide.html

Section I. Funding Opportunity Description Statutory Authority Public Health Service Act, Section 307 [42 U.S.C. 242l], as amended.

1. Background and Purpose Most emerging infectious diseases are zoonotic in origin, and close contact between humans and animals contributes to spillover events and novel public health threats. Specifically, the Democratic Republic of Congo (DRC) experiences ongoing incidents of zoonotic disease, including the highest annual burden of human monkeypox (MPX) and re-occurring outbreaks of Ebola virus disease (EVD) since the 1970’s. An improved understanding of these pathogens is critical for improved capacity to respond to emerging threats and prevent infections.

Monkeypox virus (MPXV) is found in West and Central Africa, with the overwhelming majority of cases reported from the DRC. The disease can cause a significant burden in forested areas of the country with incidence rates as high as 14 cases per 10,000 people. The animal reservoir for MPXV is unknown; however, several mammal species have been associated with MPXV. Also, human infections have been associated with exposure to wildlife products, including bushmeat.

After primary transmission from a wildlife source, MPXV can be transmitted person-to-person, with occupational infections among healthcare workers frequently reported. The lack of smallpox vaccination and unavailability of personal protective equipment (PPE) has been noted as a hindrance to investigating MPX cases by healthcare workers.

MPX is a notifiable condition in the DRC, meaning every case should be investigated with specimens collected for confirmation at the national reference laboratory in the capital of the DRC, Kinshasa. In 2011, CDC supported a cooperative agreement with the Kinshasa School of Public Health (KSPH) to enhance MPX surveillance in Tshuapa Province, resulting in a 20-fold increase in the number of MPX cases formally investigated. There has been noted improvement in surveillance and laboratory diagnosis of MPX in the DRC since then, but the risk of unreported epidemic disease and translocation into neighboring countries (Republic of the Congo, Sudan, Uganda, Rwanda) remains significant. Additional studies have been launched to better understand human interactions with wildlife, examine the natural history of suspected reservoirs, evaluate novel rapid diagnostic assays, and assess the effectiveness of a newer smallpox vaccine in healthcare workers. Without having a better understanding of the causes and prevention strategies of human MPXV infections in the region, it is difficult to determine prevention messages, appropriate preparedness strategies, and health policies.

Ebola virus disease (EVD) is a rare but fatal disease that is also transmitted to humans from wildlife. DRC has had more than 10 confirmed outbreaks of EVD, including the world’s second largest outbreak, in Eastern DRC during 2018-2020. Control of EVD outbreaks traditionally requires strong case management, infection control, contact tracing, and community engagement.

Recently developed vaccines, monoclonal antibodies, and diagnostics have further improved outbreak response in DRC. Ebola virus is known to persist in the body after recovery and can cause long-term sequalae and recrudescence of symptoms that start new outbreaks. Additional studies of risk factors, antibody persistence, clinical treatments, and genetic sequences of EVD survivors are necessary to further understand these phenomena.

Research supported by this NOFO should specifically aim to collect scientific data and evidence in the DRC to fill scientific knowledge gaps in the following areas:

Effectiveness of clinical interventions to reduce the burden of MPX and other zoonotic diseases

Development of laboratory infrastructure and policies to identify cases of MPX and other zoonotic disease more quickly and accurately

Improving understanding of how MPXV and other zoonotic viruses are maintained in sylvatic reservoirs and transmitted to humans

Determining if community interventions and vaccination preparedness plans can reduce the scale of zoonotic disease outbreaks

Durability of Ebola virus antibody reactivity over time, and any modifying factors, including impact from administration of monoclonal antibodies

Improved understanding of EVD disease recrudescence

Health Equity:

CDC supports efforts to improve the health of populations disproportionately affected by infectious diseases by maximizing the health impact of public health services, reducing disease incidence, and advancing health equity.

A health disparity occurs when a health outcome is seen to a greater or lesser extent between populations. Health disparities in infectious diseases are inextricably linked to a complex blend of social determinants that influence which populations are most disproportionately affected by these infections and diseases.

Social determinants are conditions in the places where people live, learn, work, and play that affect a wide range of health and quality-of life-risks and outcomes (https://www.cdc.gov/socialdeterminants/index.htm). These include conditions for early childhood development; education, employment, and work; food security, health services, housing, income, and social exclusion. Health equity is a desirable goal that entails special https://www.cdc.gov/socialdeterminants/index.htm efforts to improve the health of those who have experienced social or economic challenges. It requires:

Continuous efforts focused on elimination of health disparities, including disparities in health and in the living and working conditions that influence health, and

Continuous efforts to maintain a desired state of equity after health disparities are eliminated.

Applicants should use data, including social determinants data, to identify communities within their jurisdictions that are disproportionately affected by infectious diseases and related diseases and conditions, and plan activities to help eliminate health disparities. In collaboration with partners and appropriate sectors of the community, applicants should consider social determinants of health in the development, implementation, and evaluation of specific efforts and use culturally appropriate interventions and strategies that are tailored for the communities for which they are intended.

Healthy People 2030 and other National Strategic Priorities This work should contribute to accomplishing the following CDC Healthy People 2030 goal: Improve health by preventing, detecting, and responding to public health events worldwide.

Public Health Impact The research implemented through this NOFO should inform and yield effective implementation strategies to strengthen public health surveillance systems, expand laboratory utilization, and develop capacity among healthcare workers and communities capable of responding to zoonotic disease events. These activities align with CDC priorities to promote surveillance and global health to prevent the international spread of disease and control them at the source.

Relevant Work

1. Lash RR, DS Carroll, CM Hughes, et al. Effects of georeferencing effort on mapping monkeypox case distributions and transmission risk. International Journal of Health Geographics 2012; 11: 23. doi:10.1186/1476-1072X-1111-1123.

2. Bass J, Tack DM, McCollum AM, et al. Enhancing health care worker ability to detect and care for patients with monkeypox in the Democratic Republic of the Congo. Int Health 2013; 5:237-243.

3. Stanley WT, LW Robbins, JM Malekani, et al. A new hero emerges: another exceptional mammalian spine and its potential adaptive significance. Biology Letters 2013; 9, 20130486

4. Nakazawa YG, GL Emerson, H Zhao, et al. Phylogenetic and ecologic perspectives of a monkeypox outbreak, southern Sudan, 2005. Emerging Infectious Diseases 2013; 19(2):

237-245.

5. McCollum AM, Nakazawa Y, Ndongala GM, et al. Human Monkeypox in the Kivus, a Conflict Region of the Democratic Republic of the Congo. Am J Trop Med Hyg 2015;

93:718-721.

6. Monroe BP, Doty JB, Moses C, et al. Collection and Utilization of Animal Carcasses Associated with Zoonotic Disease in Tshuapa District, the Democratic Republic of the Congo, 2012. Journal of Wildlife Diseases 2015; 51:734-738.

7. Nakazawa Y, Lash RR, Carroll DS, et al. Mapping monkeypox transmission risk through time and space in the Congo Basin. PLoS One 2013; 8:e74816.

8. Nolen LD, Osadebe L, Katomba J, et al. Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo. Emerg Infect Dis 2016; 22:1014-1021.

9. Nolen LD, Osadebe L, Katomba J, et al. Introduction of Monkeypox into a Community and Household: Risk Factors and Zoonotic Reservoirs in the Democratic Republic of the Congo. Am J Trop Med Hyg 2015; 93:410-415.

10. Nakazawa Y., M Mauldin, GL Emerson, et al. A phylogeographic investigation of African monkeypox. Viruses 2015; 7(4):2168-2184

11. D Li, K Wilkins, AM McCollum, et al. Evaluation of the GeneXpert for human monkeypox diagnosis. American Journal of Tropical Medicine and Hygiene 2017; 96(2):

405-10.

12. CA Quiner, C Moses, BP Monroe, et al. Prevalence and distribution of presumptive risk factors for monkeypox in rural communities in the Democratic Republic of the Congo. PLoS ONE 2017; 12(2): e0168664.

13. L Osadebe, CM Hughes, R Shongo Lushima, et al. Enhancing the diagnostic utility of case definitions for human monkeypox in the Democratic Republic of Congo. PLoS Neglected Tropical Diseases 2017; 11(9): e0005857.

14. J Doty, J Malekani, L Kalemba, et al. Assessing monkeypox prevalence in small mammals at the human-animal interface in the Democratic Republic of the Congo. Viruses 2017; 9, 283.

15. ML Shiferaw, JB Doty, G Maghlakelidze, et al. Bridging the Divide: Creating Frameworks to Enable Inter-sectoral Collaboration for the Detection, Prevention and Control of Zoonotic Diseases. Emerging Infectious Diseases 2017; 23(13).

16. MG Reynolds, AM McCollum, B Nguete, et al. Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research. Viruses 2017; 9, 380.

17. EA Falendysz, JG Lopera, J Doty, et al. Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus anerythrus). PLOS Neglected Tropical Diseases 2017; 11(8): e0005809.

18. KN Durksi, AM McCollum, Y Nakazawa, et al. Emergence of Monkeypox — West and Central Africa, 1970–2017. Co-publication of MMWR and WER. Morbidity and Mortality Weekly Report 2018; 67: 306-10. Weekly Epidemiological Record 2018; 93:

125-32.

19. SAJ Guagliardo, MG Reynolds, J Kabamba, et al. Sounding the Alarm: Defining Thresholds to Trigger a Public Health Response to Monkeypox in the Democratic Republic of the Congo. PLoS Neglected Tropical Diseases 2018; 12(12): e0007034.

20. RH Doshi, SAJ Guagliardo, JB Doty, et al. Epidemiologic and ecologic investigations of monkeypox, Likouala Department, Republic of Congo, 2017. Emerging Infectious Diseases 2019; 25(2): 288-96.

21. BW Petersen, J Kabamba, AM McCollum, et al. Vaccinating against monkeypox in the Democratic Republic of the Congo. Antiviral Research 2019; 162: 171-7.

22. MG Reynolds, JB Doty, AM McCollum, et al. Monkeypox re-emergence in Africa: a call to expand the concept and practice of One Health. Expert Review in Anti-infective Therapy 2019.

23. J Leung, AM McCollum, K Radford, et al. Varicella in the Democratic Republic of Congo, 2009-2014. Tropical Medicine and International Health 2019; 24 (7): 839-48.

24. K Simpson, D Haymann, CS Brown, et al. Human monkeypox – after 40 years, an unintended consequence of smallpox eradication. Vaccine 2020; 38(33): 5077-81.

25. ER Whitehouse, J Bonwitt, CM Hughes, et al. Clinical and epidemiologic findings from enhanced monkeypox surveillance in Tshuapa Province, Democratic Republic of the Congo during 2011–2015. Journal of Infectious Diseases 2021; 223 (1 June): 1870-8.

26. CM Hughes, L Liu, W Davidson, et al. A tale of two viruses: co-infections of Monkeypox and Varicella-Zoster Virus in Democratic Republic of Congo. Accepted, American Journal of Tropical Medicine and Hygiene.

2. Approach The goal of this research is to identify strategies to minimize the morbidity and mortality of zoonoses of importance in the DRC, including MPX and EVD. Findings and applications developed from this project should be applicable to many areas of the DRC that are at risk of zoonotic diseases. This NOFO may fund health information systems infrastructure, including workforce and public health laboratories, to support the specific strategies, activities, and outcomes described in this NOFO.

The specific strategies for this research are as follows:

Strategies and Activities Short term outcomes Long term outcomes Strategy 1: Effectiveness of Clinical Interventions for Monkeypox and other Zoonotic Diseases in the

DRC

a. Assess the disease burden of human

MPX

b. Evaluate the effectiveness of smallpox vaccines in preventing human

MPX

c. Evaluate supportive care and therapeutic countermeasures for human MPX

Improved understanding of the burden of zoonotic disease in DRC, including high risk individuals/communities

Better understanding of short and long-term sequalae of MPX and EVD

Reduction in duration and severity of clinical MPX illness with medical countermeasures

Prevention of MPX infections via vaccine derived immunity

Improved understanding of Ebola virus persistence

Documented decrease in morbidity and mortality from MPX, EVD, and other zoonotic diseases in DRC

Reduction in recrudescent EVD illness and outbreaks

d. Evaluate the impact of EVD monoclonal antibody treatments on antibody response

e. Follow antibody production and activity in EVD survivors

f. Develop differential diagnosis for EVD recrudescence

Revised recommendations for the care and treatment of MPX and EVD patients

Strategy 2: Support of Laboratory-Based Surveillance for Monkeypox and other Zoonotic Diseases in the DRC

a. Provide support to the national reference laboratory for diagnostic testing from specimens collected in DRC and in other countries

b. Provide support for diagnostic testing at regional laboratories in affected provinces

c. Evaluate point-of-care or novel diagnostic tests for

MPX

d. Make improvements to data collection tools for zoonotic disease case investigations

e. Sequencing and phylogenetic analysis of viral isolates

Additional staff trained in laboratory diagnostics at the Provincial level

Improved timeliness in the reporting and laboratory confirmation of cases

Improved timeliness in the control of zoonotic disease following case confirmation

Laboratory testing results available to clinicians for making treatment decisions

More robust epidemiolocal data on zoonotic disease transmission

Improved knowledge of MPXV population diversity within and between geographic areas

Improved detection of MPX and EVD nationally and regionally

Validation of novel diagnostic assays that may be used for the detection of orthopoxviruses

Improved capacity to analyze viral sequence data in

DRC

Strategy 3: Investigations of Monkeypox and other Zoonotic Diseases in the

DRC

a. Qualitative and quantitative studies that explore drivers and behaviors that influence interactions with wildlife

b. Epidemiological studies to identify risk factors for transmission

c. Systematic wildlife sampling and ecological studies to characterize zoonotic disease reservoirs

d. Improving spatial data and modeling for zoonotic disease in affected provinces

e. Prospective cohort and serologic surveys of EVD survivors

f. Investigations of EVD recrudescence

Identification of human behaviors that drive zoonotic disease transmission

Identification of risk factors for primary and secondary transmission to humans

Better understanding of wildlife species that are implicated in the maintenance of a zoonotic virus

Improved maps and models for describing zoonotic disease risk in

DRC

Improved understanding of Ebola virus persistence

Identify risk factors of EVD recrudescence in survivors

EVD survivors have detectable antibodies

Reservoirs of MPX identified

Improved prevention messages for

MPX

Improved guidance for EVD survivors to prevent recrudescence

Improved understanding of the natural histories of zoonotic disease reservoirs.

Strategy 4: Outbreak Preparedness for Zoonotic Disease

a. Implement outreach to improve healthcare worker and community knowledge of zoonotic diseases

b. Improve educational resources and guides for

Increased ability to identify, report, and respond to zoonotic disease outbreaks

Improvements in case investigations, including specimen collection for laboratory confirmation

Published strategic plan for the use of vaccines to prevent MPX

Improved understanding of how prevention measures, Ability to rapidly notify, confirm, and mitigate zoonotic disease outbreaks when identified nationwide

National ownership of planning resources surveillance officials

c. Development of national pre-exposure and post-exposure vaccine plans for MPX

d. Development of evidence-based recommendations for outbreak response planning

e. Development of anticipatory guidance on EVD recrudescence including medical countermeasures, can be used in an outbreak setting

Improved guidance for EVD survivors on managing EVD disease recrudescence

Objectives/Outcomes Strategy 1: Effectiveness of Clinical Interventions for Monkeypox and other Zoonotic Diseases in the DRC

This strategy should focus on projects to improve clinical outcomes of MPX patients and prevent secondary transmission events. Specific activities could include: studies that measure the burden of MPX in target populations; prospective studies of MPX patients for long term sequalae;

evaluation of pre-exposure and post-exposure vaccination strategies; evaluation of universal supportive care regimens; evaluation of antiviral medications in treating MPX patients; and implementation of enhanced infection control practices.

Anticipated outcomes:

Completion and data collection of ongoing clinical trial of JYNNEOS smallpox vaccine to prevent MPX in healthcare workers from Tshuapa Province

Development, approval, and implementation of study protocols for post-exposure JYNNEOS smallpox vaccine study in conjunction with CDC and government authorities in the DRC

Development, approval, and implementation of study protocols for use of investigational antiviral drugs in conjunction with CDC and government authorities in the DRC

Development, approval, and implementation of study protocols for MPX and EVD supportive care regimens in conjunction with CDC and government authorities in the

DRC

Development, approval, and implementation of study protocols to evaluate the impact of monoclonal antibodies on the onset and durability of EVD antibody response

Health facilities capable of performing clinical studies and implementing any improvements necessary to sustain effective projects identified

All enrolled EVD survivors offered antibody testing for Ebola virus upon enrollment to the survivor program

Differential diagnosis and risk factors of EVD recrudescence identified

Strategy 2: Support of Laboratory-based Surveillance for Monkeypox and other Zoonotic Diseases in the DRC

This strategy should focus on strengthening of laboratory diagnosis capacity for MPX in DRC at the national, provincial, and health facility level. Specific activities could include: improvements to laboratory facilities, equipment, and safety initiatives; workforce training for laboratory staff;

deployment of diagnostic tests and regional labs; validating and piloting novel diagnostic tests;

and genetic sequencing of MPX virus. Successful activities should lead to shorter intervals between MPX infection and confirmation an overall increase in the number of confirmed cases nationally.

Anticipated outcomes:

Regional laboratories are evaluated on their ability to support diagnostic testing for MPX and quality control is provided with in-country support

MPX cases are notified, investigated, and confirmed in Tshuapa and Tshopo Provinces Rapid diagnostic tests for MPX are evaluated against a gold standard laboratory-based

PCR

Improved data collection tools are used for investigating MPX cases Improvements are obtained for understanding of viral population diversity within and among regions in DRC and Africa

Strategy 3: Investigations of Monkeypox and other Zoonotic Diseases in the DRC

This strategy should focus on projects that investigate how MPX virus is maintained in wildlife and the factors associated with primary zoonotic transmission to humans. Activities should be focused in forested communities where reliance on wildlife for food is common. Specific activities could include: collection of wildlife samples for diagnostic testing; ecological studies examining the natural histories of suspected reservoirs; anthropological studies investigating human-wildlife relationships in hunting, nutrition, and commerce; epidemiological studies to identify risk factors of human transmission; landscape and spatial analysis of MPX case locations; and improvements to local capacity to conduct animal studies safely and ethically.

Successful activities should lead to better understanding of epidemiological, ecological, and environmental risks for primary transmission and additional viral isolates from wildlife to advance the understanding of MPX reservoirs and viral dynamics.

Anticipated outcomes:

Perform multi-year ecological investigations of target species that could play a role in the maintenance of MPXV or other zoonotic diseases

Develop MPX isolate collection that represents diverse sources including various animal species, locations, and/or temporal periods

Conduct studies of human behaviors and bushmeat value chains in communities affected by MPX and other zoonotic diseases to better understand their interactions with wildlife and products originating from wildlife

Establish workgroup that will be responsible for the development and implementation of a national Institutional Animal Care and Use Committee (IACUC) in the DRC

Mobilize a team that will be responsible for generating more accurate geographic data for Tshuapa Province

Identify risk factors for primary and secondary human transmission of MPX Conduct serosurveys of EVD survivors to determine durability/longevity of antibody reactivity, antibody viral neutralization and cellular response Understand the role EVD antibody production has on disease recrudescence Identify risk factors for EVD recrudescence through laboratory investigations, interviews, and clinical examinations

Strategy 4: Outbreak Preparedness for Zoonotic Disease

This strategy should focus on activities that assist DRC and other affected countries respond to outbreaks of MPX quickly and effectively. These activities should be coordinated with national partners in Kinshasa but can occur in affected provinces across DRC. Specific activities can include convening workshops with key stakeholders to develop response planning materials;

training of public health workforce on MPX; evaluating educational strategies to increase community and healthcare worker knowledge of MPX; and modelling response scenarios for different vaccination strategies. Successful activities should lead to faster identification and mitigation of MPX outbreaks nationwide.

Anticipated outcomes:

Additional members of the public health workforce are trained to recognize MPX and respond appropriately

Models based on MPX surveillance and clinical research data are developed to guide use of JYNNEOS vaccine in a post-exposure setting

Affected communities and healthcare workers are educated about MPX leading to increased reporting and investigation of MPX cases

National response plans are developed from surveillance and research data on disease occurrence and prevention measures

Anticipatory guidance and educational materials on disease recrudesce are developed and available for EVD survivors and public health officials

Target Population The project should be carried out completely in the DRC and activities for MPX should be based primarily in Tshuapa Province. Other provinces that regularly report cases of MPX could also be considered. Populations of special interest include healthcare workers, persons with frequent wildlife contact (hunters, butchers, market sellers), and residents of forested communities due the potential for increased zoonotic risk of MPX. Laboratory, preparedness, and coordination activities could occur in the national capital, Kinshasa.

Activities for other zoonotic diseases should be based primarily in provinces with recently confirmed cases of EVD (Equateur, Ituri, North Kivu, South Kivu). Populations of special interest are survivors of previous EVD infections and their close contacts. Laboratory, preparedness, and coordination activities could occur in the national capital, Kinshasa.

Collaboration/Partnerships Successful implementation of this project will require working relationships with several key partners in country, including the Ministry of Health, Institut National de Recherche Biomédicale (INRB, National Laboratory), University of Kinshasa, and the National Laboratory for Veterinary Diagnostic Research. The application may also identify partner(s) with expertise to perform community and healthcare worker outreach and education, and topic-specific program implementation.

Evaluation/Performance Measurement The application should include measurable goals and aims based on a five (5)-year research project period. The application should describe specific, measurable, achievable, realistic, and time-phased (SMART) project objectives for each activity described in the application’s project plan and describe the development and implementation of project performance measures based on specific programmatic objectives.

Strategy 1: Effectiveness of Clinical Interventions for Monkeypox and other Zoonotic Diseases in the DRC

The proposed evaluation measures for Strategy 1 are:

Identify field sites and hire key staff to coordinate surveillance, clinical studies, and laboratory testing. Staffing plans and contracts should be submitted annually for review.

Ensure that all research study protocols receive human subjects approval by an accredited Institutional Review Board (IRB) prior to the project start date

Prepare and implement a research protocol to evaluate an antiviral treatment regimen against MPXV

Conduct enrollment and follow-up of EVD survivor cohorts Present results of research studies to local, national, and regional public health authorities in a timely fashion Attend monthly conference calls with CDC staff and other project partners

Strategy 2: Support of Laboratory Surveillance for Monkeypox and other Zoonotic Diseases in the DRC

The proposed evaluation measures for Strategy 2 are:

Ensure that mechanisms and agreements are in place to ship specimens from field sites to INRB at a minimum of four times per year

Support enhanced surveillance for human MPX in Tshuapa Province by ensuring at least 70% of notified cases each month are investigated by trained staff and appropriate samples are collected

Implement a program of diagnostic testing at selected provincial laboratories by ensuring all staff are properly trained, oversight is provided by the national lab, and equipment is maintained appropriately

Provide records to document maintenance of project vehicles, motors, and equipment Ensure that appropriate specimens at INRB are tested withing 30 days of receipt with results shared with CDC and submitting jurisdictions

Strategy 3: Investigations of Monkeypox and other Zoonotic Diseases in the DRC

The proposed evaluation measures for Strategy 3 are:

Document all ecology studies involving vertebrate animals and ensure that all study staff have been trained to handle animals following CDC approved IACUC protocols

Provide accurate geographic data for all sites visited as part of clinical and ecological research projects

Provide accurate lists of all animal specimens and ecological data collected within 30 days of any field work

Provide notes of any animal welfare workgroups to CDC for review within 10 days of the event

Summarize enrollment data for research studies quarterly

Strategy 4: Outbreak Preparedness for Zoonotic Diseases in the DRC

The proposed evaluation measures for Strategy 4 are:

Provide reports on community education within 30 days of event Provide copies of training/educational materials and national agencies prior to any training event Provide evaluations of all healthcare worker trainings within 30 days of event

Translation Plan Research findings from this project should be made available to national and regional public health officials via oral presentations, written reports, recommendation documents, and published manuscripts in the scientific literature.

3. Funding Strategy N/A

Section II. Award Information Funding Instrument Type:

CA (Cooperative Agreement)

A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed:

New - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding:

$3,500,000

Estimated Total Annual Budget Period Funding, including direct and indirect costs:

Year 1: $700,000 Year 2: $700,000 Year 3: $700,000 Year 4: $700,000 Year 5: $700,000

Anticipated Number of Awards:

Estimated total funding available for the first year (first 12 months), including direct and indirect costs: $700,000

Estimated total funding available for the entire project period, including direct and indirect costs: $3,500,000

Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling:

$700,000 Per Budget Period

Award Floor:

$500,000 Per Budget Period

Total Period of Performance Length:

5 year(s)

Throughout the Period of Performance, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this NOFO.

If you are successful and receive a Notice of Award, in accepting the award, you agree that the award and any activities thereunder are subject to all provisions of 45 CFR Part 75, currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category:

25 (Others (see text field entitled "Additional Information on Eligibility" for clarification))

Additional Eligibility Category:

Other:

Foreign Organizations: a Foreign Organization is a public or private organization, whether non-profit or for-profit, located in a country other than the United States (U.S.) and its territories that is subject to the laws of the country in which it is located, irrespective of the citizenship of project staff or place of performance.

2. Foreign Organizations Foreign Organizations are eligible to apply.

Foreign (non-US) organizations must follow policies described in the HHS Grants Policy Statement (http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. International registrants can confirm DUNS by sending an e-mail to ccrhelp@dnb.com, including Company Name, D-U-N-S Number, and Physical Address, and Country. Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: https://eportal.nspa.nato.int/ AC135Public/Docs/US%20Instructions%2 0for%2 0NSPA%20NCAGE.pdf.

Foreign components of U.S. Organizations are eligible to apply.

For this announcement, applicants may include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Additional Information on Eligibility The Kinshasa School of Public Health (KSPH) is the only eligible applicant.

4. Justification for Less than Maximum Competition CDC is seeking a uniquely qualified partner for this award with the following attributes: 1) A public institution with established close ties to the national public health system, including the Democratic Republic of the Congo's (DRC's) national laboratory; 2) demonstrated expertise in managing clinical studies with associated adverse event monitoring in remote areas; 3) scientific expertise in ethically capturing wildlife, conducting species identification to the appropriate https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf mailto:ccrhelp@dnb.com https://eportal.nspa.nato.int/AC135Public/Docs/US%20Instructions%20for%20NSPA%20NCAGE.pdf taxonomic level, and collecting appropriate samples to optimize viral detection; 4) sustained management of field sites in areas highly endemic for monkeypox; and 5) previous experience in managing financial assistance in the form of a CDC cooperative agreement.

The Kinshasa School of Public Health (KSPH) is the only public institution in DRC that meets the requirements to implement this research cooperative agreement based on the following:

1. KSPH was the first indigenous academic institution in DRC devoted to public health education and research. KSPH has a unique role in the public health system of DRC by being both an institute of the University of Kinshasa and previously serving as the bone fide agent of the Ministry of Health (MOH). Hence, KSPH is directly affiliated with both the principle academic research institution in DRC (whose faculty have expertise in public health, ecology, and medicine) and with those units within the MOH that conduct infectious disease surveillance, provide laboratory diagnostic support, implement vaccinations, and perform medical product reviews (essential for clinical studies). KSPH also maintains an Institutional Review Board (IRB) in the DRC that has active DHHS registration and federal assurance policies governing the ethical conduct of scientific research.

2. KSPH was the implementing partner for an open label trial of JYNNEOS smallpox vaccine in the healthcare workers of Tshuapa Province (2017-present), a study that will continue under the new cooperative agreement. By conducting this study, KSPH gained experience in stakeholder engagement and input on the operational requirements for the protocol, obtaining ethical and regulatory approvals, improving and maintaining cold chain and specimen storage infrastructure, and securely maintaining confidential data. Under a previous agreement, KSPH purchased, transported, and installed a network of solar refrigerators and freezers capable of safe and reliable storage of vaccines and human specimens by using established relationships in rural Tshuapa Province. The replacement of this infrastructure by a new grantee would come at a significant cost to the government.

3. KSPH and their partners at the University of Kinshasa have 10 years of experience in conducting rigorous investigations of potential monkeypox reservoir species. This includes faculty, students, and technicians who received direct training from CDC scientists on IACUC-approved ethical and humane animal collection and sampling procedures. KSPH staff and partners have also developed relationships with community leaders, hunters, traders, and market sellers that allow for ecological field work and detailed anthropologic interviews to better understand human interactions with wildlife. KSPH partners also maintain a network of camera traps, and a local weather station, to collect environmental data remotely from Tshuapa Province.

4. KSPH has continually maintained a field office in Tshuapa Province devoted to monkeypox surveillance and research since 2011. During this tenure, KSPH staff provided training and supervision to local human and animal health authorities, implemented research projects, and investigated outbreaks of zoonotic diseases. KSPH staff provide a situational report on monkeypox to CDC each month. This longstanding commitment to working in this area has yielded the most thorough longitudinal dataset on monkeypox incidence globally since smallpox eradication. No other indigenous or foreign institution has been able to sustain a continual field site for this length of time in a monkeypox-endemic area of DRC.

5. KSPH has a well-established record of accomplishment of successful partnerships with CDC and other USG partners, including previous awards CK11-003/CK14-002/CK17- 002 which served as precursors to this research NOFO. KSPH has staff trained in both the scientific (public health, medicine, biology) and administrative skills (accounting, logistics, project management) necessary to manage discretionary assistance and are well-versed in CDC's financial and reporting requirements.

Disapproval of this single source competition NOFO would create a significant setback in monkeypox surveillance and research in DRC because: 1) no other entities in DRC have the combination of scientific expertise, DRC Ministry of Health support, previous experience, trained staff, and infrastructure with a well-established field site to complete this work successfully; 2) it may take five or more years to build a similar research capacity in the region;

3) it would be extremely challenging for other organizations to cultivate the strong relationships KSPH has established with regulatory authorities, public health officials, and international partners both in Kinshasa and at the field site in Tshuapa Province; 4) it will cost more in federal financial support to establish the infrastructure and staffing that exist in KSPH by a new awardee; 5) CDC will lose access to the established monkeypox surveillance systems in Central Africa; and 6) a lapse in this research required to establish new infrastructure and partnerships by a new awardee would cause a substantial global loss in scientific advancement and outbreak preparedness, potentially resulting in increased unnecessary morbidity and mortality.

5. Responsiveness If the applicant requests a funding amount greater than the ceiling as indicated in Section II. of this NOFO, HHS/CDC may consider the application non-responsive.

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

PLEASE NOTE: For applications due on or after April 4, 2022, applicants must have a unique entity identifier (UEI) at the time of application submission. In preparation for the federal government’s April 4, 2022, transition from the Data Universal Numbering System (DUNS) to the Unique Entity Identifier (UEI), applicants must obtain a UEI. The UEI is generated as part of SAM.gov registration. Current SAM.gov registrants have already been assigned their UEI and can view it in SAM.gov and grants.gov. Additional information is available on the GSA website, SAM.gov, and Grants.gov-Finding the UEI.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code:

https://eportal.nspa.nato.int/AC135Public/Docs/US Instructions for NSPA NCAGE.pdf

System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, SAM.gov.

https://www.gsa.gov/about-us/organization/federal-acquisition-service/office-of-systems-management/integrated-award-environment-iae/iae-systems-information-kit/unique-entity-identifier-update https://sam.gov/content/home https://grantsgovprod.wordpress.com/2021/09/14/how-to-find-an-applicants-uei-within-grants-gov/ https://sam.gov/content.gov

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The one-time registration process will take three to five days to complete.

However, it is best to start the registration process at least two weeks prior to application submission.

All Senior/Key Personnel (including Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing Principal Investigator (PD/PI) eRA Commons account is affiliated with the eRA commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the eRA Commons registration process at least four (4) weeks prior to the application due date. ASSIST requires that applicant users have an active eRA Commons account in order to prepare an application. It also requires that the applicant organization's Signing Official have an active eRA Commons Signing Official account in order to initiate the submission process.

During the submission process, ASSIST will prompt the Signing Official to enter their Grants.gov Authorized Organizational Representative (AOR) credentials in order to complete the submission, therefore the applicant organization must ensure…