A19. 75D301-24-R-72894.pdf

BAA 75D301-24-R-72894

CENTERS FOR DISEASE CONTROL AND

PREVENTION (CDC)

BROAD AGENCY ANNOUNCEMENT

(BAA)

75D301-24-R-72894

APPLIED RESEARCH TO ADDRESS

EMERGING PUBLIC HEALTH

PRIORITIES

ISSUANCE DATE: February 9, 2024 CLOSING DATE: March 15, 2024

TABLE OF CONTENTS

PART I - INTRODUCTION

Authority Process

Step 1 - E-mail Contact (Technical Dialogue) Step 2 - Informal White Paper (Technical Dialogue) Step 3 - Submission of Formal Research Proposal Step 4 - Contract Award for Selected Projects

Government Obligation

BAA Points of Contact

PART II CDC RESEARCH INTERESTS

OVERVIEW

Topic 1: Developing data and analytical applications for public health using generative and conversational artificial intelligence (AI) (OPHDST)……………………………………...….………………………………….8

Topic 2: Use of Graph Methodologies for Disease Ontologies, Data Standardization, and Epidemiological Surveillance (OPHDST)

Topic 3: Methods, workflows, and architectures to establish and facilitate Machine Learning Operations (MLOps) (OPHDST)……………………………………………………

Topic 4: Identifying strategies to strengthen community clinical linkages for people with diabetes and prediabetes (NCCDPHP)…………………………….…………………………………….……………….….…10

Topic 5: Innovations in Anopheles stephensi surveillance, control, and genomics (NCEZID)

Topic 6: Advancing the control of dengue vectors by applying novel persistent, long-lasting larvicides or insect growth regulators (NCEZID)..…………………………………………………………….…………

Topic 7: Innovative approaches to pathogen agnostic infectious disease surveillance, culture-independent sequencing, and multi-pathogen bioinformatic and data integration (NCEZID)………………..…………...13

Topic 8: Novel methods to control or prevent bites by Ixodes scapularis ticks (NCEZID).…….………..….15

Topic 9: Advancing Fungal Disease Surveillance: Integrating Longitudinal Treatment and Outcome Data for Enhanced Public Health Insights (NCEZID)………………………………………………………….……15

Topic 10: Wastewater surveillance applications and knowledge gaps (NCEZID)

Topic 11: Metagenomic studies to better characterize the ecological distribution of endemics (NCEZID)..17

Topic 12: Novel methods to assess the burden of pneumococcal disease among populations at increased risk

(NCIRD)………………………………………………………………………..…………….……………………18

Topic 13: Strengthening pertussis surveillance and diagnostics by improvements in antigen production

(NCIRD)…………………………………………………………………………....……….……………………..19

Topic 14: Group A Streptococcus (GAS) disease incidence and genetic relatedness in populations disproportionately affected by GAS (NCIRD)……………………………………………..………….………..19

Topic 15: Advanced Genomic and AI-Driven Diagnostic Solution for Rapid Detection of Infectious Diseases

(ORR)………………………………………………………………………………..………..…………………...20

Topic 16: Next-Generation AI-Driven Community Contact Tracing and Exposure Notification for Enhanced Disease Control (ORR)……………………………………..…………….…………………………21

Topic 17: Assessing the difficulty of producting infectious select agent postive RNA viruses from genomic material (ORR)………………………………………………………………………………………………

PART III - WHITE PAPER SUBMISSION

Use of Non-Government Personnel White Paper Evaluation Criteria

White Paper Format and Content White Paper Submission

PART IV - PROPOSAL PREPARATION AND SUBMISSION

General Information Eligibility Post-Employment Conflict of Interest Restrictive Markings on Proposals Non-U.S.Citizen Participation Period of Performance Contract Types

Cost Certification……………………………………………………………………………………………..…27 Funding

Proposal Submission Follow-On Contracts Proposal Copies Mailing Addresses

Proposal Preparation Instructions Section I - Technical Section Contents Section II - Administrative Section Contents

Contract Type Environmental Considerations Organizational Conflicts of Interest Disclosure Requirement Understanding of Evaluation Policy Representations, Certifications and Other Statements of Offerors Offeror's Performance Assessment Rating (CPARS)… ……………………………………………..…... 32 Past Performance………………………………………………………………………………………… 32 Subcontracting Plan Title to Equipment Section III - Cost Section Contents Period of Performance Direct Labor Materials Other Direct Costs Travel Subcontracts Consultants Miscellaneous Indirect Costs Fee/Profit

PART V - PROPOSAL EVALUATION

Initial Review Scientific Review

Proposed Research Potential Contribution Offeror’s Qualifications

Personnel Cost Realism Administrative Proposal

Proposal Comparisons

PART VI - PROPOSAL FORMS and ATTACHMENTS

PART I - INTRODUCTION

Authority

The Centers for Disease Control and Prevention (CDC), the Office of Science (OS) issues this Broad Agency Announcement (BAA) under the provisions of FAR 35.016 and FAR 6.102(d)(2) which provides for the competitive selection of research proposals. Contracts that are awarded based on responses to this BAA are as a result of full and open competition and therefore in full compliance with the provisions of PL 98-369, "The Competition in Contracting Act of 1984."

The CDC may award contracts with educational institutions, nonprofit organizations, not for profit organizations, state and local government, and private industry for research and development (R&D) in those areas covered in Part II of this BAA.

Within the meaning of FAR 6.102 and 35.016, this announcement constitutes the government’s solicitation for this effort. There will be no other solicitation issued in regard to this requirement.

Offerors should be alert for any BAA amendments that may be posted on beta.SAM.gov.

Process

Priorities and funding for CDC research initiatives are determined each fiscal year. Potential offerors are encouraged to contact the respective CDC BAA technical point of contact noted in the table below to determine whether their research may warrant the submission of a white paper. For all email inquiries to the Subject Matter Expert Technical POC, please copy the CDC BAA Technical Coordinator as well.

The following four-step sequence is established for offerors contemplating submission of a white paper or a proposal under this BAA. This sequence allows for an early determination of the potential for interest based on technical merit, applicability to CDC and projected funding. This process is designed to limit offeror and Government expenditure of effort to prepare and review formal proposals for research that may have little chance of being funded.

Step 1 – Email Contact (Technical Dialogue)

Once the BAA is announced, technical dialogue can begin. Technical dialogue between the Government and the potential offeror is the first step. The initial point of contact may direct offerors to a specific scientific/technical point of contact based on the topic area and specifics of the proposed research project.

The initial contact points for each area of research interest identified in Part II is listed below.

Research Interests Technical Point of Contact

(POC)

POC e-mail address

Topic 1. Developing data and analytical applications for public health using generative and conversational artificial intelligence (AI)

(OPHDST)

Daniel K. Addyson utw3@cdc.gov

Topic 2. Use of Semantic Knowledge Graphs for Disease Ontologies, Data Standardization, and Epidemiological Surveillance (OPHDST) Daniel K. Addyson utw3@cdc.gov

Topic 3. Methods, workflows, and architectures to establish and facilitate Machine Learning Operations (MLOps) (OPHDST) Daniel K. Addyson utw3@cdc.gov

Topic 4. Identifying strategies to strengthen community clinical linkages for people with diabetes and prediabetes in communities that experience disparities in diabetes outcomes linked with unfair and

Bryce Smith bli1@cdc.gov unjust social, economic, and environmental disadvantages

(NCCDPHP)

Topic 5. Innovations in Anopheles stephensi surveillance, control and genomics (NCEZID)

Audrey Lenhart Sarah Zohdy ajl8@cdc.gov ykr2@cdc.gov

Topic 6. Advancing the control of dengue vectors by applying novel persistent, long-lasting larvicides or insect growth regulators to household containers that accumulate water and produce Aedes mosquitoes (NCEZID)

Robert Barrera amz9@cdc.gov

Topic 7. Innovative approaches to pathogen agnostic infectious disease surveillance, culture-independent sequencing, and multi-pathogen bioinformatic and data integration (NCEZID)

Eleanor Click Samantha Katz eoc9@cdc.gov goy3@cdc.gov

Topic 8. Novel methods to control or prevent bites by Ixodes scapularis ticks (NCEZID)

Lars Eisen evp4@cdc.gov

Topic 9. Advancing Fungal Disease Surveillance: Integrating Longitudinal Treatment and Outcome Data for Enhanced Public Health Insights (NCEZID)

Anastasia Litvintseva frq8@cdc.gov

Topic 10. Wastewater surveillance applications and knowledge gaps

(NCEZID)

Amy Kirby agk1@cdc.gov

Topic 11. Metagenomic studies to better characterize the ecological distribution of endemics (NCEZID)

Anastasia Litvintseva frq8@cdc.gov

Topic 12. Novel methods to assess the burden of pneumococcal disease among populations at increased risk (NCIRD)

Lesley McGee Miwako Kobayashi afi4@cdc.gov ydk3@cdc.gov

Topic 13. Strengthening pertussis surveillance and diagnostics by improvements in antigen production (NCIRD)

Panagiotis Maniatis Sundaram (Ajay) Vishwanathan vhd2@cdc.gov ile0@cdc.gov

Topic 14. Group A Streptococcus (GAS) disease incidence and genetic relatedness in populations disproportionately affected by GAS

(NCIRD)

Christopher Gregory Yuan Li hgk4@cdc.gov yqh8@cdc.gov

Topic 15. Advanced Genomic and AI-Driven Diagnostic Platform for Rapid Detection of Infectious Diseases (ORR)

Jana Austin aun6@cdc.gov

Topic 16. Next-Generation AI-Driven Community Contact Tracing and Exposure Notification for Enhanced Disease Control Diseases

(ORR)

Jana Austin aun6@cdc.gov

Topic 17. Assessing the difficulty of producing infectious select agent positive RNA viruses from genomic material (ORR)

Joshua Graves qsx6@cdc.gov

Step 2 – Submission of Informal White Paper (Technical Dialogue)

This step is a continuation of the technical dialogue for projects of interest. Submission of a white paper does not require an explicit request or invitation from CDC. Offerors may submit a white paper even if there was no technical dialogue with the technical/scientific point of contact and/or Subject Matter Expert (SME).

The white paper can be no more than 4 pages in length, all inclusive. Any white paper response that exceeds 4 pages may be considered ineligible for evaluation. The purpose of the white paper is to facilitate the SME’s understanding of the scientific and technical aspects of the proposed research project. Use of the white paper is intended to determine which efforts are of sufficient scientific and technical merit prior to submission of a formal research proposal as described in Part IV; therefore, informal white papers should not be so lengthy or detailed as to constitute a formal proposal (see Part IV). Informal white papers should contain a Rough Order of Magnitude (ROM) (e.g. “Estimated Cost”). A ROM is NOT a full-blown business proposal. Instead, it is merely a “statement or a range” that provides a high-level estimate of what the offeror believes the project will cost.

NOTE: Unless noted with the topic, CDC will not discuss budget estimates or number of awards expected and cannot review draft white papers prior to submission.

Please note that the Government may use non-Government participants during the white paper review process (See Part III – Use of Non-Government Personnel).

All submitted white papers will undergo an initial review for technical merit and program applicability.

See Part III for specific evaluation criteria.

NOTE: Once white papers are submitted technical dialogue STOPS!

Step 3 - Submission of Formal Research Proposal

If sufficient interests in a proposed research project exists the Contracting Officer will invite (in writing) the white paper submitter to offer a formal research proposal (See Part IV). Continued communications after request for proposal receipt may make offerors ineligible for award.

Please note that the Government may use non-Government participants during the evaluation of the proposals technical section (See Part III – Use of Non-Government Personnel).

Step 4 - Contract Award for Selected Projects

The primary basis for selecting proposals for award shall be scientific/technical merit, importance to agency programs, corporate capabilities, and personnel. Cost realism, reasonableness and fund availability will also be considered to the extent appropriate. Past performance will also be considered. Any contract resulting from this process will include all standard FAR clauses or the appropriate alternates applicable to the contract type for the proposed project and offeror institution. See Part V for specific evaluation criteria. The Government has the right to make multiple awards.

NOTE: Projects will be funded as contracts or OTA (Other Transaction Authority) Agreements, NOT

GRANTS.

Government obligation

Persons submitting white papers and proposals are cautioned that only a Contracting Officer may obligate the Government to any contract involving expenditure of Government funds. The Government is under no obligation to pay for the cost of the development of white papers or proposals. Furthermore, there is no commitment on behalf of the Government to fund any proposal. Offerors are cautioned that the submission of a white paper and a proposal is strictly on a voluntary basis.

BAA POINTS OF CONTACT

CDC’s BAA Technical Coordinator and point of contact is Diana Bartlett, MPH, MPP who may be reached by email at dbartlett@cdc.gov.

CDC’s BAA Contracting Officer points of contact are listed below. Please include Mr. Michael Crow in any correspondence related to this announcement.

Name Email Mr. Michael Crow wyv2@cdc.gov mailto:dbartlett@cdc.gov mailto:wyv2@cdc.gov

PART II - CDC RESEARCH INTERESTS

Overview The Centers for Disease Control and Prevention (CDC) works to protect the U.S. from health, safety and security threats, both foreign and domestic. Specifically, CDC works with its partners to monitor health, detect and investigate health problems, conduct research to enhance and implement prevention strategies, develop and promote sound public health policies, promote healthy behaviors, foster safe and healthful environments, respond to current and emerging threats, and

CDC’s role as the nation’s health protection agency is to operate 24/7 in order to keep people healthy and safe. The agency accomplishes this goal by working to detect and respond to new and emerging health threats; address the biggest health problems causing death and disability; move science and advanced technology into actions to prevent disease; promote health and safe behaviors, communities and environments; develop leaders by training the public health workforce; and understand the health pulse of the nation.

For this announcement, CDC is requesting white papers for the following research interest areas, which are further described below:

Office of Public Health Data Surveillance and Technology (OPHDST)

Topic 1. Developing data and analytical applications for public health using generative and conversational artificial intelligence (AI) (OPHDST)

Generative and conversational Artificial Intelligence (AI) is a new technology that is rapidly developing and becoming quickly ubiquitous in many digital applications. Numerous technology companies are now developing their own generative AI algorithms, particularly large language models (LLMs), that allow users to both interact with pre-built models in a turn-based, conversational manner; as well as train, refine, & extend pre-built models for their own specific needs and use cases. LLMs focus on text generation, but generative AI is also being extended to image, sound, and video.

This topic aims to solicit research that demonstrates novel and innovative ways to protect the health of our communities and advance public health insights and action through conversational and generative AI.

Our primary areas of interest include (but are not limited to):

a. Using pre-built models to conduct research and develop applications for information summarization, extraction and retrieval (e.g., chatbots, recommendation engines), for both enterprise- and public-level interaction.

b. Adopting methodologies, best practices, and pilots to extend, train, tune, and/or refine pre-built open-source models for CDC- and public health domain-specific uses.

c. Implementing strategies and architectures to build, test, and deploy both generative AI models and their associated application interfaces.

d. Develop and test methodologies to identify and mitigate various types of biases and misinformation introduced by conversational and generative AI.

Research Objectives include:

a. Training large language models for public health, CDC, or other topic-specific uses, particularly Natural Language Processing (NLP) solutions for development and review of legal documents (e.g., contracts and data use agreements)

b. Identify and pilot novel use cases and applications for CDC and public health use, particularly in the following areas:

1. To promote interoperability, data standardization and mapping of clinical and administrative codes between healthcare entities (between private and public partners, state, tribal, local, and territorial (STLT) partners and federal/CDC partners), particularly for laboratory testing and other clinical data.

2. Linking different data systems, such as AI-generated crosswalks across surveillance tools and intra-facility data sources.

3. AI-assisted text extraction from images, such as optical character recognition (OCR) and mapping to standardized data structures and vocabularies.

4. Search, synthesis, and interpretation of public health-related legal and policy documentation.

5. Develop systems, architectures, and pipelines for enterprise deployment of these models

Total award value for all awards in this topic area will not exceed $1 million.

Topic 2. Use of Graph Methodologies for Disease Ontologies, Data Standardization, and Epidemiological Surveillance (OPHDST)

The increasing availability of a multitude of data types in the public health domain (population, clinical, laboratory, and other) from a variety of sources and partners, requires new methodologies to identify, capture, store, and analyze increasingly complex relationships between these data. Graph methodologies such as semantic knowledge graphs (SKG) provide the ability to accomplish this for a wide variety of purposes.

Graph database and analytics technologies provide a dynamic and scalable way to store, retrieve, and visualize data elements in a holistic manner. Incorporating this capability represents an innovative and critical need for modernizing CDC’s and the public health data infrastructure.

The purpose of this topic is to seek innovative solutions and methods, particularly using SKGs, to improve public health outcomes. Specifically, we seek solutions that will aid in the storage, visualization, and potential connecting of diverse data sources and types, particularly combining population-level and clinical data. Additionally, we seek novel applications of graph-based methodologies in aiding health ontology and vocabularies, such as terminological standardization, refence mapping, and data cataloguing.

Our primary areas of interest include (but are not limited to):

1. Testing the feasibility of using graph-based methodologies for a diverse array of public health surveillance, response, and policy-related activities; including, but not limited to, mapping and visualizing disease or other medical codes across different standards and organizations;

identifying commonalities between legal, policy, or similar documents.

2. Assessing the utility of knowledge graphs for data management and cataloguing within CDC and with State, Tribal, Local, and Territorial (STLT) partners.

3. Proposing solutions for text extraction and representation in graph form from sources including PDF and Electronic Health Records (EHR) records

Total award value for all awards in this topic area will not exceed $1 million.

Topic 3. Methods, workflows, and architectures to establish and facilitate Machine Learning Operations (MLOps) (OPHDST)

Machine Learning Operations (MLOps) is a new and increasingly critical component of delivering analytical products, particularly for predictive and machine learning models, and Artificial Intelligence (AI). MLOps is unique to the analytics lifecycle because it combines principles and techniques of data management, data engineering, and data science to deliver continuously sustainable and scalable solutions to customers. With the increasing availability and complexity of data for analysis and surveillance of disease, the agency requires technical solutions and methodologies that can create the backbone for these processes. This topic aims to solicit research that demonstrates solutions and methods for continuous integration and delivery of data engineering and analytics services. We seek both general frameworks with public health and healthcare applicability, as well as for specific conditions and diseases; but particularly for integrating data and analytical products across public health organizations and entities, with differing levels of maturity in the data and analytics lifecycle.

Research Objectives include:

a. Data Management and Preprocessing: Investigate data quality and preprocessing techniques to ensure the accuracy and reliability of input data for machine learning (ML) models. Identify strategies for handling missing data, outliers, and data imbalances specific to public health datasets.

b. Model Development and Selection: Propose methods to improve efficiency of developing ML models, particularly across agency partners, and integrating model outputs across the agency.

Explore techniques for hyperparameter tuning and model optimization to improve predictive performance while minimizing resource usage. Investigate methods for efficient distributed training of large-scale machine learning models.

c. Deployment and Monitoring: Define strategies for deploying machine learning models into operational environments, considering factors such as latency, reliability, and security. Propose methods to integrate data pipelines and model outputs across public health entities and partners.

Propose mechanisms for continuous monitoring of deployed models to detect performance degradation, concept drift, and potential biases.

d. Documentation and Knowledge Sharing: Propose best practices for flexible and rapid knowledge sharing, such as documentation-as-code. Explore ways to bridge the gap between technical and non-technical stakeholders to ensure alignment with agency goals.

Total award value for all awards in this topic area will not exceed $1 million.

National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

Topic 4. Identifying strategies to strengthen community clinical linkages for people with diabetes and prediabetes in communities that experience disparities in diabetes outcomes linked with unfair and unjust social, economic, and environmental disadvantages (NCCDPHP)

Community Clinical Linkages (CCL) are connections between community and clinical sectors that aim to improve health within a community. When implemented, they are an effective, evidence-based approach to preventing and managing chronic diseases such as diabetes. CCL also help address health equity by ensuring that people with diabetes and prediabetes have access to the resources and support they need to prevent, delay, or manage the condition. Despite the evidence supporting the effectiveness of CCL, there are barriers to implementation within the health care, public health and community settings.

This topic aims to describe barriers and facilitators to CCL and identify effective implementation models and strategies in communities that experience disparities in diabetes outcomes linked with unfair and unjust social, economic, and environmental disadvantages.

The objectives for this research are:

a. Identify and describe barriers and facilitators to community clinical linkages in diabetes care.

b. Identify and describe factors that support and sustain effective connections between community and clinical sectors including infrastructure and capacity support (e.g. staffing, evaluation, subject matter expertise).

c. Identify and test strategies to build community clinical linkages that engage systems, practitioners and community representatives in evidence based approaches (including Diabetes Self-Management Education and Support Services and the National DPP) to providing care and support to people with diabetes who experience disparities in diabetes outcomes.

National Center for Emerging Zoonotic and Infectious Diseases (NCEZID)

Topic 5: Innovations in Anopheles stephensi surveillance, control, and genomics (NCEZID)

An invasive malaria vector, Anopheles stephensi, endemic to south Asia, has been detected in Africa and significant increases in malaria have been associated with its establishment. This mosquito is unlike native African malaria vectors in that it is urban adapted, thrives in artificial containers, persists throughout dry periods, and has been found to be resistant to insecticides used in malaria control efforts.

Anopheles stephensi is considered a biological threat to global malaria control efforts potentially broadening the landscape of malaria transmission from primarily rural to urban settings, reversing progress towards malaria elimination. It is predicted that an additional 126 million people in urban areas will be at risk of malaria if An. stephensi continues to spread throughout the African continent. In order to develop a strategy to halt the spread of An. stephensi and limit its impacts on global malaria, it is essential to determine the extent of its distribution on the continent, how it is being introduced and spreading, and the feasibility of approaches to control, contain, or eliminate the species from non-endemic areas.

Enhanced surveillance for An. stephensi is currently limited, and the only way to confirm suspect An.

stephensi detections is through molecular sequencing. Information about where invasive populations came from and how they are spreading is largely unknown. This information is necessary to determine the feasibility of containment or elimination of the invasive species in non-endemic areas. The most common malaria vector control interventions, insecticide treated bed nets (ITNs) and indoor residual spraying (IRS), target biting and resting behaviors of native vectors that thrive in rural environments and have highly seasonal populations. Anopheles stephensi, however, is a competent and urban-adapted malaria vector that thrives in artificial containers and persists throughout dry periods, therefore, different vector control approaches are needed to combat the species. First detected in Djibouti in 2012, An. stephensi is now well established in the country and an over 30-fold increase in malaria has been reported since its initial detection. Following detection in Djibouti, An. stephensi was reported from Ethiopia (2016), Sudan (2016), and Somalia (2019), Nigeria (2020) and in early 2022 the first urban malaria outbreak associated with An. stephensi was reported in Ethiopia during the dry season. A modeling study reported a potential 50% increase in Plasmodium falciparum malaria in Ethiopia if the vector continues to spread in country, which would cost an estimated $72 million dollars per year in vector control interventions alone.

Detections in 2022 and early 2023 confirmed its spread into Nigeria, Eritrea, Kenya and Ghana. Recent research has shown that invasive An. stephensi in Ethiopia are found in artificial containers, are resistant to pyrethroid, carbamate, and organophosphate insecticides, are competent vectors of the human malaria parasites in circulation in Ethiopia, at this point in time are best surveyed through larval surveillance and collection of resting adults near animal shelters, have been found harboring infective malaria parasites, and have been confirmed from 45 urban and rural locations.

Here, we welcome activities that would 1) use population genomics to determine the feasibility of containment and elimination approaches for An. stephensi by determining where invasive An. stephensi is coming from, how long populations have been in their current locations, how long it takes populations to establish, and how An. stephensi is being introduced and spreading through non-endemic areas; 2) develop innovative vector surveillance and control strategies that can target invasive An. stephensi populations, enabling national programs to respond rapidly and effectively to the threat of An. Stephensi;

and 3) identify and expand on opportunities to integrate An. stephensi surveillance and control efforts with those of other vector borne diseases through integrated vector surveillance and management approaches. Taken together, these topics will allow for a comprehensive, data-driven response to the biological threat of An. stephensi on global malaria.

There is an urgent need for strong molecular entomology capacity for the rapid confirmation and reporting of An. stephensi in non-endemic regions, and once confirmed, population genomics can be used to determine whether populations are newly established and where they came from. Through this objective, population genomics from invasive An. stephensi will be used to understand the spread of this vector and determine whether eliminating An. stephensi in non-native areas is possible.

Specifically, these questions could include, but are not limited to:

a. From where did invasive An. stephensi populations originate?

b. How is An. stephensi being introduced?

c. How long have An. stephensi populations been established in different locations?

d. Are there continuous reintroductions?

e. Where will An. stephensi likely invade next?

f. How can capacity for surveillance, control, and genomics for other vectors (e.g. Aedes) be leveraged to respond to the threat of An. stephensi?

Understanding the bionomics of An. stephensi is critical to developing effective surveillance and control strategies with the greatest likelihood of success. Specific activities could include, but are not limited to, basic bionomic research and piloting control tools and strategies in both experimental and field settings.

Opportunities to leverage successful Aedes surveillance and control activities to further target An.

stephensi are a priority.

Topic 6. Advancing the control of dengue vectors by applying novel persistent, long-lasting larvicides or insect growth regulators to household containers that accumulate water and produce Aedes mosquitoes (NCEZID)

Suppression of dengue vectors, such as Aedes aegypti and Aedes albopictus and the pathogens they transmit to people in urban areas, requires limiting the production of new mosquitoes in aquatic containers habitats, which can be locally abundant and diverse. Although there is a variety of effective products that either kill or suppress the development of immature Aedes mosquitoes, their duration in the aquatic environment (weeks) is shorter than the length of time that mosquitoes can survive as dormant embryos in a quiescence or diapause state (months) waiting to hatch and complete their immature development. Another limitation of current larvicides or growth inhibitors is that when the water in the container is tossed away, the control agent is lost. For these reasons, the use of current larvicides or growth inhibitors requires frequent reapplications that are difficult to achieve under limited-resource conditions.

A control agent that surpasses the length of time the eggs of Aedes are viable in the environment and that is retained in the container even is the water is tossed away, is expected to keep inhibiting the production of adult mosquitoes for nine months, with significant reductions of reapplication times and product. Some products may be more amenable as long-lasting agents to control Aedes in aquatic containers. For example, Juan et al. 2013 (https://doi.org/10.1603/ME12249) prepared containers to be used as ovitraps made out of beeswax or paraffin: stearin with pyriproxyfen that was 100% effective at controlling immature Ae. aegypti for one year under laboratory conditions. It will be important to develop a method of application of the product that sticks to the inner surface of containers but that cannot be removed or lost.

The objective of this topic is to improve the control of dengue vectors through the development and testing of new formulations and delivery systems of long-lasting inhibitors of mosquito development and emergence from water-filled containers.

Some strategies could include, but are not limited to:

a. Development of a long-lasting formulation and an efficient delivery system of a larvicide or insect growth regulator that will suppress the emergence of new Aedes mosquitoes under field conditions without significant loss of the product (e.g., stuck to the inner walls/bottom of the container), in several frequent and important aquatic containers in Puerto Rico. There are useful (e.g., buckets, plant trivets) and junk (e.g., old appliances, used tires) containers that accumulate water that is not for human or animal consumption, which produce Aedes mosquitoes in yards of residences and abandoned lots that could be treated with a persistent, long-lasting control agent. It is important that the control agent persists on the inner walls or bottom of the container even if the water in the container is changed or dries out.

b. Investigating what factors modulate the effectiveness of the suppression approach developed under this topic of dengue vectors in containers under varied but common environmental conditions in Puerto Rico such as, but not limited to exposure to the sun, water turnover, and dry cycles.

c. Developing and testing a standard operating procedure for field applications.

Topic 7. Innovative approaches to pathogen agnostic infectious disease surveillance, culture-independent sequencing, and multi-pathogen bioinformatic and data integration (NCEZID)

Advances in pathogen genomics, bioinformatics and genomic epidemiology are rapidly transforming public health practice, and are changing traditional approaches to prevention, control, and response to many infectious disease threats. These new technologies are both flexible and powerful, and while they can be applied to many critical areas of infectious disease detection, characterization, surveillance and response, they are also data intensive and technically complicated, requiring specialized skills and infrastructure to be used most effectively. This can be challenging in many public health settings, where access to specialized resources and expertise may not always be feasible. Innovative solutions are critically needed to help improve access, interoperability and portability of these important new technologies, and to lower the technical complexity and other barriers for routine use in domestic and global public health settings, and in the field.

For this topic area, we are inviting proposals that advance pathogen agnostic detection and improve the speed and actionability of data for tracking and halting transmission of new and emerging pathogens.

This includes rapid molecular, genomic or multi-omic detection and characterization of pathogens, and the incorporation of these data with clinical and epidemiologic data to assess their transmission within populations, to better align sequencing with routine diagnostic specimens in public health, clinical practice and at the point of need and in the development of flexible and cost-effective laboratory and sample acquisition workflows.

Priority research areas of interest include:

a. Advance flexible, pathogen-agnostic approaches for infectious disease detection, characterization and public health surveillance.

Advances in one or more of the following areas: 1) rapid classification, tracking, identification and/or characterization of pathogens utilizing multi-pronged genomic and/or biomarker-based (e.g., other “-omic”) approaches. Solutions may include tools that can be prepositioned to support early threat detection and rapid tracking/intervention, as well as tools that can be rapidly customized (e.g. based on genomic characterization) and deployed for screening, tracking, and diagnosis of pathogens and infectious diseases. 2) evaluation of new or optimized specimen types (e.g., clinical, environmental) including types that can be rapidly and non-invasively sampled (e.g., breath) ideally with workflows feeding into surveillance systems (e.g., for early threat warning) or supporting specific use cases (e.g., respiratory or bloodborne disease of unknown etiology); 3) approaches that streamline pathogen agnostic tool automation, decrease workflow complexity, and limit overall consumable requirements and cost; 4) technical and logistical solutions to enable pathogen genomic surveillance or outbreak investigation in conjunction with laboratory, at-home or field rapid diagnostic tests (e.g., repurposing remnant test specimens); 5) open-source software and other tools supporting pathogen data analysis, visualization, and triggers for alerts and reporting; 6) development of an integrated, open and flexible “sample to answer” wet laboratory method and bioinformatics technology platform that allows simultaneous processing of diverse pathogen samples and includes a cost-effective infrastructure model to support the system's scalability; and 7) solutions to reduce contamination and improve quality assurance so that pathogen genomic data can be easily prepared for sharing. Systems that can provide real-time monitoring for sequencing and bioinformatic workflows, including both laboratory and field settings are of particular interest. Tools and methods to improve the performance of sequence-based pathogen identification and characterization under regulated settings – including both the development and submission of new assays for regulatory approval, as well as tools to simplify CLIA-compliant microbial sequencing in regulated laboratory settings.

b. Develop tools to improve sample collection, sequencing, bioinformatic and genomic epidemiologic analyses from culture-independent diagnostic test samples and platforms. Advances in one or more of the following areas: 1) workflows for genomic sequencing, bioinformatic and other analysis direct from culture-independent diagnostic test samples or platforms (e.g., remnant materials); 2) linkage of genomic tools, such as those developed as part of this topic or already available, to the functionality of pathogen databases (e.g., MicrobeNet, etc.) or other existing services to enhance passive surveillance capabilities. Analytic tools for prediction of the source or geographic origin of pathogens or to identify anomalous patterns are of particular interest. Solutions that allow linking of data and outputs from clinical laboratories to departments of public health for public health decision-making are also of interest.

c. Improve open source, interoperable tools and systems for data integration and portable, reproducible bioinformatics, analytics and data visualization for infectious disease public surveillance and response.

Develop a comprehensive bioinformatics and data integration framework that enables seamless combination of epidemiologic, genomic, geospatial, and other relevant data types as well as tools that enable better data visualization. Of particular interest are systems designed for scalability and cost efficiency. Pre-packaged, standardized, scalable, and deployable bioinformatics solutions for multiple pathogen groups are also of interest.

We anticipate issuing 6 to 8 awards for this topic contingent upon the availability of funding, with a range of $500,000 to $3,000,000 depending on project objectives, scope, duration, impact and complexity.

Topic 8. Novel methods to control or prevent bites by Ixodes scapularis ticks (NCEZID)

Tickborne diseases pose a serious threat to public health. They account for over 75% of reported vector-borne disease cases in the United States and incidences of tickborne diseases continue to increase with cases reported over an expanding geographic region. The majority of infections are spread by Ixodes species ticks. In the eastern United States Ixodes scapularis is the primary vector for several medically significant pathogens including Borrelia burgdorferi s.s., Borrelia mayonii, Borrelia miyamotoi, Anaplasma phagocytophilum, Ehrlichia muris eauclairensis, Babesia microti, and Powassan virus.

Existing personal protection measures and environmentally based tick/pathogen control methods have not proven adequate to stem the rising tide of tick-borne diseases. Novel methods with potential to reduce human bites by pathogen-infected I. scapularis could be of great public health benefit.

Specific topics of interest include:

a. Novel approaches to reduce the probability that a tick encounter will result in a human bite.

b. Novel approaches for control of host-seeking ticks.

c. Novel approaches for control of ticks on key reproductive hosts (particularly deer) and/or pathogen reservoirs (particularly rodents).

We expect to award up to 3 awards for this topic. Total award value for all awards will not exceed $1million.

Topic 9. Advancing Fungal Disease Surveillance: Integrating Longitudinal Treatment and Outcome Data for Enhanced Public Health Insights (NCEZID)

The research objectives of this study are to understand the ecological distribution of endemic fungal species within a designated ecosystem. Specifically, the project aims to identify and quantify the diversity and abundance of these species, elucidate their functional roles and interactions within the ecosystem, and assess potential relationships between endemics and broader ecosystem health. Studies that can offer real-time, data-driven strategies will provide dynamic insights into treatment effectiveness, disease trends, and risk factors, enabling timely interventions and evidence-based recommendations for the management of fungal diseases.

Studies are encouraged to include the following, but are not limited to:

a. Methods that incorporate treatment and patient outcomes with surveillance systems

b. Methods to gather accurate estimations of morbidity and mortality rates associated with fungal diseases

c. Assess the effectiveness of different treatment strategies

Topic 10. Wastewater surveillance applications and knowledge gaps

The National Wastewater Surveillance System (NWSS) was established in 2020 to provide community-level surveillance for SARS-CoV-2 that is independent of healthcare or testing access. Since 2020, NWSS has expanded to represent over 40% of the US population with sampling sites in all 50 states and 7 Tribal Nations. In addition to trends in SARS-CoV-2 infections, NWSS also provides data on SARS-CoV-2 variants and mpox infections, and some NWSS sites are testing for additional pathogens. More information on NWSS is available at https://www.cdc.gov/nwss/index.html.

Wastewater surveillance uses quantitative molecular assays to measure the concentrations of pathogens of interest in wastewater. By assessing the concentrations over time, trends in community infections can be detected. Interpretation of the wastewater data is limited by lack of understanding of other inputs into the wastewater system, as well as range and median time periods for clinical shedding and environmental stability data for the pathogens of interest. Questions remain about the feasibility, interpretation, and resource efficacy of wastewater surveillance in non-community or non-sewered systems (e.g., surveillance for facilities or in communities primarily using septic systems).

The research areas outlined below seek to fill critical knowledge gaps that will allow wastewater surveillance to be used more broadly and with greater rigor for public health. Offerors are encouraged to submit white papers that address any of the areas below.

a. Respiratory Virus Sequencing from Wastewater

SARS-CoV-2 sequencing has been shown to be a powerful tool for detecting emerging variants of concern and understanding the movement of variants across the US. CDC is interested in evaluating the utility of sequencing for influenza virus and respiratory syncytial virus (RSV). The primary goal of this additional sequencing would be to identify circulating strains; however, detection of mutations impacting diagnostic testing, vaccines, or therapeutics is also relevant. Laboratory and bioinformatic approaches are of interest. Proposals that include evaluation of the relationship between wastewater sequencing data and clinical genomic data will be prioritized. Studies could include methods that are virus specific, such as tiled amplicon sequencing, or non-targeted such as metagenomic sequencing and may address one or both target viruses. Targets in addition to influenza virus and RSV will be considered as funding allows.

Proposals that only address SARS-CoV-2 or rely on deep sequencing without considerations for cost effective solutions will not be considered.

b. Animal Input into Wastewater Systems

Although sewered wastewater systems effectively capture and contain human waste, input from other animals does occur. When this happens, it can skew wastewater surveillance data by inflating the wastewater strength or input measure (if non-human specific, such as flow or total suspended solids) or inflating the pathogen concentration (if the pathogen has animal reservoirs). This animal input into wastewater system is particularly challenging for pathogens with significant zoonotic carriage, such as influenza virus and limits the interpretation of wastewater surveillance data.

CDC seeks proposals to better understand and account for non-human animal input into wastewater systems. Research would address animal inputs that are relevant to respiratory viruses, but a broader approach to animal sources would be considered. Laboratory-based and modeling approaches could be included. Research should also consider both point and non-point source contributions as well as sample-or site-level methods that detect changing animal inputs over time at a site.

c. Alternative Applications of Wastewater Surveillance

Wastewater surveillance has proven to provide consistent, actionable data for sewered communities. CDC is interested in evaluating the utility of wastewater surveillance beyond sewered communities (e.g., facility-based testing in non-sewered communities). CDC seeks proposals to evaluate the utility of alternative applications of wastewater surveillance. Proposals that focus on airplanes, cruise ships, or other means of global and domestic travel are out of scope. Utility is defined as generating data that is actionable to protect the health of the population being tested. Proposals could include development or validation of sampling and laboratory testing methods, implementation schemas to assist decisionmakers, data analysis and modeling methods appropriate for these applications, ethical considerations, or economic analyses. Proposals that include a cost-benefit analysis of the alternative method compared to existing surveillance (clinical and/or community wastewater surveillance) are preferred.

d. Shedding of Respiratory Viruses into Wastewater

Understanding fecal and urinary shedding of respiratory viruses, specifically SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV), is important for interpreting wastewater surveillance data for these infections. Quantitative measurements in stool and urine over the full time-course of infection, from individuals representing a range of demographic profiles, and illness severities, could help map wastewater measurements to community infection burden and help understand the potential for wastewater measurements to lead other surveillance indicators, such as reported cases and syndromic surveillance. However, few quantitative wastewater-relevant viral shedding data are published, and capturing fecal and urinary shedding dynamics over the full course of infection is challenging. CDC seeks research that could provide quantitative data on virus levels in human stool, urine and other wastewater-relevant sources for SARS-CoV-2, influenza virus, and/or RSV over the full time-course of infection, including samples from individuals representing a range of demographic profiles, vaccination status, and illness severities. The study could consider measuring genomic copies per unit using molecular tools.

Quantitative sample and laboratory controls, including matrix recovery controls and endogenous fecal microbial controls, are encouraged. In particular, data between the period of infection and illness onset, and data from asymptomatic individuals, are desired as well as viral variant data. Characterizing stool composition, including solids content, would be beneficial. Proposals utilizing archived samples will be considered as well.

Topic 11. Metagenomic studies to characterize the ecological distribution of endemics (NCEZID)

This topic seeks research that incorporates metagenomic techniques to assess its ability to comprehensively characterize the ecological distribution of endemic species within a specific ecosystem.

By analyzing DNA sequences from environmental samples, metagenomic research seeks to uncover these unique organisms' diversity, abundance, and interactions, providing insights into their roles in ecosystem dynamics and potential impacts on local biodiversity and ecosystem health.

Advanced DNA sequencing techniques can introduce a cutting-edge approach to uncovering the intricate relationships between endemic species and their ecosystem context. This novel methodology can reveal previously unexplored species interactions, functional roles, and their implications for ecosystem dynamics.

A better comprehension of these species' roles in ecosystem dynamics can shed light on potential vectors of diseases or beneficial…