CDC BAA 75D301-20-R-67837; Amendment 0001.pdf

BAA 75D301-20-R-67837

(Amendment 0001)

CENTERS FOR DISEASE CONTROL AND

PREVENTION (CDC)

BROAD AGENCY ANNOUNCEMENT (BAA)

75D301-20-R-67837

ORIGINAL ISSUANCE DATE: November 22, 2019

CLOSING DATE: January 7, 2020

TABLE OF CONTENT

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: Increasing Engagement of Persons Living With Prediabetes and at high risk for developing type 2 diabetes in the National Diabetes Prevention Program (DPP) Lifestyle Change Program (NCCDPHP)……8

Topic 2: Developing novel intervention methods for tick and mosquito-borne disease (NCEZID)…………..9

Topic 3: Antibiotic Resistance (AR) Pathogens and Clostridium difficile infection (CDI) (NCEZID)……...11

Topic 4: Development, implementation and deployment of data management system for curation and reporting of annual Neisseria gonorrhoeae whole genome sequence data (NCHHSTP)……………………………………11

Topic 5: Approaches to prevention and control of bacterial vaccine-preventable diseases (NCIRD)……

Topic 6: Developing information needed to advance Legionnaires’ disease prevention (NCIRD)…………..13

Topic 7: Surveillance for non-invasive pneumococcal pneumonia (NCIRD)………………………………….14

Topic 8: Use Modeling and Forecasting Tools to Improve the U.S. Response to Seasonal and Pandemic Influenza

(NCIRD)……………………………………………………………………………………………………………14

Topic 9: Address Critical Gaps in Knowledge of the Total Preventive Benefit of Influenza Vaccines

(NCIRD)…………………………………………………………………………………………………………….15

Topic 10: Virology, Surveillance and Diagnosis Branch in the Influenza Division, NCIRD, CDC is seeking technologies that will improve vaccines through in-depth virus characterization and by identifying/selecting optimal candidate vaccine viruses(NCIRD)………………………………………………………………………18

Topic 11: Innovative laboratory and analytic methods to confirm influenza transmission within households and describe influenza viral diversity (NCIRD/ID)……………………………………………………………..Deleted

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 Reporting Requirements Non-U.S.Citizen Participation

Period of Performance Contract Types

Cost Certification………………………………………………………………………………………………..23

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 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

Funding of research within CDC will be determined by funding constraints and research priorities set during each fiscal year. Therefore, those contemplating submission of a white paper are encouraged to contact the

CDC BAA technical point of contact as noted below to determine whether the research warrants further inquiry.

If the research warrants further inquiry and if funding is available, then submission of a white paper/proposal will be entertained. 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 issued, technical dialogue can began. 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 SME Technical POC

Email

Topic # 1: Increasing Engagement of Underserved Persons Living With Prediabetes and at high risk for developing type 2 diabetes in the National Diabetes Prevention Program (DPP) Lifestyle Change Program (NCCDPHP)

1.1: Development and evaluation of innovative methods, tools, and strategies to address Social Determinants of Health in a way that increases access to enrollment and/or retention of underserved persons in the National DPP Lifestyle Change

Program.

Bryce Smith Bsmith6@cdc.gov mailto:Bsmith6@cdc.gov

1.2: Development and evaluation of innovative incentive-based methods, tools, and strategies to increase enrollment and retention of underserved persons in the National DPP

Lifestyle Change Program.

Bryce Smith Bsmith6@cdc.gov

Topic #2: Developing novel intervention methods for tick and mosquito-borne disease (NCEZID)

2.1: Novel approaches to suppress tick vectors, disrupt natural transmission of tick-borne pathogens and prevent human tick bites

Lars Eisen

VBDBAA@cdc.gov

2.2: Improved understanding of (i) tick- or human behavior-related factors leading to increased risk of human contact with tick vectors and (ii) specific roadblocks leading to limited use of existing personal protective measures and environmentally based tick/pathogen control methods.

Lars Eisen

VBDBAA@cdc.gov

2.3: Transmission-blocking human vaccines targeting the tick or the pathogen

Lars Eisen VBDBAA@cdc.gov

2.4: Targeted mosquito control and evaluation of mosquito control adulticides

Roxanne Connelly VBDBAA@cdc.gov

Topic #3: Antibiotic Resistance (AR) Pathogens and Clostridium difficile infection (CDI)(NCEZID)

3.1: Risk Factors for transmission of AR pathogens and CDI in community settings.

Alexander Kallen Akallen@cdc.gov

Topic # 4: Development, implementation and deployment of data management system for curation and reporting of annual Neisseria gonorrhoeae whole genome sequence data (NCHHSTP)

4.1: Develop a data management system for the receipt, curation, and reporting of Neisseria gonorrhoeae isolate and sequence data elements.

Kim Gernert

Brian Raphael nin1@cdc.gov elx9@cdc.gov

Topic #5: Approaches to prevention and control of bacterial vaccine-preventable diseases (NCIRD/DBD/MVPDB)

5.1: Establish human challenge model of Bordetella pertussis infection to accelerate new pertussis vaccine development and licensure

Susan Hariri Shariri@cdc.gov

5.2: Evaluate evolving transmission dynamics of circulating

Bordetella pertussis under different vaccination strategies

Michael Weigand mweigand@cdc.gov

Removed – Amendment 0001

5.3: Evaluate molecular characteristics of invasive isolates of H. influenzae, compared to carriage isolates from household contacts of patients and a control population

Sara Oliver Seoliver@cdc.gov

Removed – Amendment 0001

5.4: Evaluate H. influenza vaginal carriage among pregnant females

Sara Oliver seoliver@cdc.gov

Added – Amendment 0001

5.5: Evaluate cell-mediated immune response to natural pertussis infection and compare to immune response to pertussis vaccination

Susan Hariri shariri@cdc.gov

Topic #6: Developing information needed to advance Legionnaires’ disease prevention (NCIRD/DBD/RDB)

6.1: Development and evaluation of a rapid test to determine the presence of viable Legionella pneumophila within environmental samples

Todd Raziano Traziano@cdc.gov mailto:Bsmith6@cdc.gov mailto:VBDBAA@cdc.gov mailto:VBDBAA@cdc.gov mailto:VBDBAA@cdc.gov mailto:VBDBAA@cdc.gov mailto:Akallen@cdc.gov mailto:nin1@cdc.gov mailto:elx9@cdc.gov mailto:Shariri@cdc.gov mailto:mweigand@cdc.gov mailto:Seoliver@cdc.gov mailto:seoliver@cdc.gov mailto:shariri@cdc.gov mailto:Traziano@cdc.gov

6.2: Investigating possible genetic or other factors associated with increased survival of Legionella bacteria to heat, disinfectants, biocides, and other common remediation tools in water systems

Todd Raziano Traziano@cdc.gov

6.3: Enhancing whole genome sequencing data from clinical isolates of non-Lp1 bacteria to both increase our understanding of these less commonly identified strains and to augment domestic and international sequencing databases

Todd Raziano Traziano@cdc.gov

Topic #7: Surveillance for non-invasive pneumococcal pneumonia (NCIRD/DBD/RDB)

7.1: Establish active pneumococcal urine antigen testing in adults 18 years of age or older with chest x-ray confirmed pneumonia in a defined catchment area.

Tamara Pilishvili tdp4@cdc.gov

Topic #8: Use Modeling and Forecasting Tools to Improve the U.S. Response to Seasonal and Pandemic Influenza

(NCIRD/ID)

8.1: Pandemic Forecasting Challenge: Fund independent 3rd party to simulate data for a synthetic pandemic forecasting challenge

Matt Biggerstaff Mbiggerstaff@cdc.gov

Topic #9: Address Critical Gaps in Knowledge of the Total Preventive Benefit of Influenza Vaccines (NCIRD/ID)

9.1: Clinical Research Networks to Improve Clinical

Management of Hospitalized Influenza Patients Tim Uyeki Tuyeki@cdc.gov

9.2 Innovative methods to evaluate the role of influenza vaccines in attenuating severe disease in adults Manish Patel mpatel@cdc.gov

9.3 Innovative methods to improve estimates of influenza

vaccine effectiveness for different influenza vaccine types.

Mark Thompson mthompson@cdc.gov

9.4 Innovate approach to assess health utilization in the

population.

Melissa Rolfes Mrolfes1@cdc.gov

9.5 Identifying regional factors associated with influenza virus circulation and vaccine effectiveness.

Manish Patel mpatel@cdc.gov

Topic #10: Strategies/technologies to improve selection and/or development of influenza candidate vaccine viruses

(NCIRD /ID/VSDB)

10.1 Strategies/technologies that will advance vaccines through improved virus characterization, and/or optimal candidate vaccine virus (CVV) development

Lindsay Culp lculp@cdc.gov

Removed – Amendment 0001

Topic #11: Innovative laboratory nd analytic methods to confirm influenza transmission within households and describe influenza viral diversity (NCIRD/ID)

11.1 Innovative laboratory and analytic methods to

confirm influenza transmission within households and describe influenza viral diversity

Melissa Rolfes Mrolfes1@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 whie paper even if there was no techincal dialogue with the SME. Additionally, from time to time, the scientific point of contact may request that an offeror submit an informal white paper. The white paper can be no more than 4 pages in length. 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 mailto:Traziano@cdc.gov mailto:Traziano@cdc.gov mailto:tdp4@cdc.gov mailto:Mbiggerstaff@cdc.gov mailto:aul3@cdc.gov mailto:mpatel@cdc.gov mailto:mthompson@cdc.gov mailto:Mrolfes1@cdc.gov mailto:mpatel@cdc.gov mailto:lculp@cdc.gov mailto:Mrolfes1@cdc.gov 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: CDC cannot 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 there is sufficient interest in a proposed research project, the Contracting Officer will invite the offeror to submit a formal research proposal (see Part IV). During the preparation of the offeror’s proposal, technical dialogue may resume. The purpose of the technical dialogue is to facilitate the Government’s understanding of the scientific and technical aspects of the proposed research project. However, once proposals are submitted, communication between scientific personnel and the technical review team STOPS!

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

All proposals will receive an initial review (see Part V) and the Contracting Officer will notify the offeror, in writing, whether the proposal will be processed for award. 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, 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 for the development of white papers or proposals. Furthermore, there is no commitment on behalf of the Government to fund any proposal. Contractors are caution that the submission of a white paper and a proposal is submitted strictly on a voluntary bases.

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.

Based on the research topic area, CDC has multiple contractual points of contact. The POCs and the research areas they are responsible for is listed below.

mailto:dbartlett@cdc.gov

Name Research Topic Area Telephone Number Email

Ms. Ashia Everett #6, #7 404-498-5229 oiv4@cdc.gov

Mr. Chad Pickett #8 404-498-2958 pvt4@cdc.gov

Ms. Paula Taylor #9, #10 770-488-2433 vga8@cdc.gov

Mr. Ronnie Williams #1, #5 404-498-2594 oga3@cdc.gov

Mr. Tim Williams #2, #3, #4 770-488-2791 tpw8@cdc.gov mailto:oiv4@cdc.gov mailto:pvt4@cdc.gov mailto:vga8@cdc.gov mailto:oga3@cdc.gov mailto:tpw8@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 provide public health leadership and training.

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 areas, which are further described below:

Topic #1: Increasing Engagement of Persons Living With Prediabetes and at high risk for developing type 2 diabetes in the National Diabetes Prevention Program (DPP) Lifestyle Change Program

(NCCDPHP)

Approximately 84 million Americans have prediabetes, nearly 1 in 3 adults. Prediabetes is characterized by blood glucose levels that are higher than normal but not high enough to be diagnosed as type 2 diabetes. People with prediabetes have an increased risk of developing type 2 diabetes, heart disease, and stroke.

The CDC-led National Diabetes Prevention Program (National DPP:

http://www.cdc.gov/diabetes/prevention/index.html) is a public/private partnership working to scale and sustain an evidence-based lifestyle change program (LCP) for people with prediabetes to prevent or delay onset of type

2 diabetes. The LCP is founded on the Diabetes Prevention Program research study and subsequent translation studies which showed that making achievable behavior changes helped participants lose 5% to 7% of their body weight and reduced the risk of developing type 2 diabetes by 58% (by 71% for people 60 years and older). The

CDC-recognized LCP consists of a minimum of 16 weekly, then a minimum of six monthly group sessions conducted over a year. A trained lifestyle coach facilitates the sessions to guide people in changing their lifestyle and losing weight.

Research has shown that the more sessions of an LCP a person attends, the better the outcomes. National DPP

LCPs have identified retaining people in their sessions, especially after the initial 16 weeks, as a challenge.

Analysis of National DPP evaluation data has demonstrated significant dropout at different points of the program.

Since the National DPP was launched in 2012, over 1,700 organizations have provided the lifestyle change program to over 400,000 people at high risk for type 2 diabetes. But with 84 million people living with prediabetes, we need to reach millions of participants to stem the tide of type 2 diabetes.

Given the vast number of people living with prediabetes and the availability of an effective intervention, CDC is seeking the development and evaluation of innovative methods, tools, and strategies to increase recruitment and enrollment into the National DPP Lifestyle Change Program, particularly for underserved populations.

While novel delivery methods and mechanisms are welcome, the content, number of sessions, and length of the intervention (12 months) cannot be changed as those are all essential elements in the original and translational research which has found the program to be effective.

1.1: Development and evaluation of innovative methods, tools, and strategies to address Social

Determinants of Health in a way that increases access to enrollment and/or retention of underserved persons in the National DPP Lifestyle Change Program (NCCDPHP).

1.2: Development and evaluation of innovative incentive-based methods, tools, and strategies to increase enrollment and retention of underserved persons in the National DPP Lifestyle Change Program

(NCCDPHP).

Topic #2: Developing novel intervention methods for tick and mosquito-borne disease (NCEZID)

CDC seeks to improve the overall knowledge and control of the U.S.’s Vector-borne Disease burden. The

Division of Vector Borne Disease will issue a BAA to solicit proposals that harness scientific research and innovation to enhance the ability to control vector-borne diseases. This effort will address knowledge gaps regarding the control of Lyme disease and Arboviral diseases. CDC anticipates that the knowledge resulting from awards made under this announcement will contribute significantly to the evidence base for prevention and control of vector-borne diseases.

Toward these objectives, CDC has identified four areas of interest:

2.1: Novel approaches to suppress tick vectors, disrupt natural transmission of tick-borne pathogens and prevent human tick bites (NCEZID).

In the absence of human vaccines against tick-borne pathogens in the United States, prevention of tick-borne diseases depends on other personal protective measures and environmentally based tick/pathogen control methods. Ongoing geographic range expansion of important tick vectors (particularly Ixodes scapularis and Amblyomma americanum) has led to increased ranges as well as overall burden of their associated diseases (particularly Lyme disease, anaplasmosis, babesiosis, and ehrlichiosis). As currently used, existing personal protective 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 tick bites and tick-borne diseases could be of great public health benefit. Methods with potential to impact multiple tick vector species and multiple disease agents are of particular interest.

Specific topics of interest include but are not restricted to:

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

• Novel approaches to disrupt feeding on humans by undetected ticks, including anti-tick vaccines.

• Novel approaches for control of host-seeking ticks with killing efficacy similar to currently used synthetic pesticides but with more favorable environmental profiles.

• Oral systemic acaricides for long-lasting tick bite protection of key reproductive hosts

(particularly deer) and/or pathogen reservoirs (particularly rodents).

• Oral reservoir-targeted vaccines against Lyme disease spirochetes for key natural pathogen reservoirs (particularly rodents).

• Oral combination baits including both a systemic acaricide and a reservoir-targeted vaccine against Lyme disease spirochetes for key natural pathogen reservoirs (particularly rodents).

• Novel devices for improved delivery (topical, oral or by other means) of systemic acaricides or reservoir-targeted vaccines to key reproductive hosts (particularly deer) and/or pathogen reservoirs (particularly rodents).

• Deer-targeted anti-tick vaccines.

To avoid duplication with other Federal funding initiatives, applications relating to the following approach are discouraged:

• Transgenic and para-transgenic approaches in ticks or pathogen reservoirs.

2.2: Improved understanding of (i) tick- or human behavior-related factors leading to increased risk of human contact with tick vectors and (ii) specific roadblocks leading to limited use of existing personal protective measures and environmentally based tick/pathogen control methods (NCEZID).

Successful reduction of tick-borne diseases depends on the availability of effective intervention methods but also requires knowledge to inform the most effective ways of implementing specific intervention approaches and a clear understanding of roadblocks preventing their uptake.

• Determination of where host-seeking ticks occur most commonly on residential properties and within neighborhoods, to increase awareness of high-risk peridomestic and neighborhood habitats for tick encounters and potentially guide vegetation/landscape management to reduce high-quality tick habitat and suppression of host-seeking ticks.

• Determination of specific combinations of habitat (e.g., vegetation height and composition) and human behavior leading to increased risk for tick contact.

• Determination of where on the human body ticks most commonly make initial contact (to inform more effective use of tick repellents and permethrin-treated clothing).

• Knowledge, attitudes and practices/behavior (KAP/KAB) studies to determine willingness to use and pay for specific interventions, including to better understand whether homeowners are more willing to accept increased cost or increased level of vigilance and personal effort.

2.3: Transmission-blocking human vaccines targeting the tick or the pathogen (NCEZID).

Recognizing that environmentally based tick/pathogen control methods and personal protective measures are unlikely to eliminate the risk for bites by infected ticks, it is important to pursue approaches with potential to prevent transmission of a pathogen from a biting infected tick. This may be achieved in different ways, including to disrupt the tick feeding process or directly target the disease agent in the tick.

• Advancing clinical trials of existing candidate vaccines and immunotherapeutics.

• Development of novel pathogen transmission-blocking anti-tick vaccines for use in humans, targeting either a single or (ideally) multiple tick vector species.

To avoid duplication with other Federal funding initiatives, applications relating to the following approach are discouraged:

• Antigen discovery and research on adjuvants.

2.4: Targeted mosquito control and evaluation of mosquito control adulticides (NCEZID).

Recognizing that control methods can be optimized to reduce the risk for bites by infected mosquitos, it is important to pursue approaches with potential to prevent transmission of a pathogen from a biting infected mosquito. This may be achieved in different ways, including the application of chemical pesticides/adulticides to disrupt the mosquito feeding process or directly target the mosquito vector in question to reduce the overall population.

• SIT - Irradiation of Culex vectors of West Nile virus in CONUS

• Develop a smart cage for evaluating efficacy of mosquito control adulticides

Topic #3: Antibiotic Resistance (AR) Pathogens and Clostridium difficile infection (CDI) (NCEZID)

3.1: Risk factors for transmission of AR pathogens and CDI in community settings (NCEZID).

Many multidrug-resistant organisms (MDROs) and Clostridioides difficile identified in CDC’s AR

Threats Report have historically been spread primarily in healthcare settings. However, some of these pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), Extended-spectrum beta-lactamase (ESBL) and Clostridium difficile infection (CDI) have begun to spread more broadly in community settings, increasing the overall national burden of these pathogens and threatening to undermine progress in healthcare at preventing infections they cause. Furthermore, the causes of this dramatic rise in community-onset infections and risk factors for spread is unclear. The goal of this request is to define prevalence and risk factors of these pathogens in community settings in order identify and implement effective prevention strategies.

Topic #4: Development, implementation and deployment of data management system for curation and reporting of annual Neisseria gonorrhoeae whole genome sequence data (NCHHSTP)

4.1: CDC seeks to develop a data management system for the receipt, curation, and reporting of Neisseria gonorrhoeae isolate and sequence data elements (NCHHSTP).

Gonorrhea is a sexually transmitted infection that remains a major public health concern. Based on the latest surveillance, N. gonorrhoeae (NG) causes an increasing number of gonorrhea cases in the U.S. and worldwide and has progressively developed resistance or decreased susceptibility to multiple classes of antibiotics, including penicillins, sulphonamides, tetracyclines, quinolones, macrolides and cephalosporins.

These concerns have prompted CDC to conduct genomic sequencing and analysis of N. gonorrhoeae on a national level for monitoring and trends analysis of strain types and resistance mechanisms present within the U.S. CDC, through multiple surveillance and monitoring programs and through the regional Antibiotic

Resistance Laboratory Network, has the capacity to collect and sequence up to 6000 NG isolates annually, and record pertinent epidemiological, phenotypic and genotypic data per isolate.

CDC requires the development, implementation and deployment of an internal CDC data management system with the following requirements:

• Receipt, curation and archive of continuously updating data elements, aligned through project specific data identifiers.

• Data protection and control

i. Provide regulated, limited, secure user access, based on defined data ownership, and user-defined roles (internal CDC, surveillance partners).

• Data entry

i. Data elements will be received from multiple data sources (both internal CDC and external sites) (input data sources: database, portal download, JSON, excel or CSV files, etc.), defined data structure. Provision of GUI for data entry.

• Quality control

i. Provide check and balance systems to ensure data quality and ensure completeness of data.

ii. Perform calculations as required upon data input, calculate interpretations, accommodate re-processing samples and re-entry of data elements.

iii. Curator review and approval. Periodic audit of data, data quality, email notifications.

• Interpretation and reporting

i. Searchable queries, multiple layer queries, and development of customized reports.

ii. Dashboard for periodic (weekly, monthly and annual) reviews and reports, trend analyses of data. Development of reports for surveillance partners.

iii. Provision of GUI for database query and reporting.

• Internal and External data management

i. Archive file storage location of whole genome sequence and derivative files.

ii. Implement national-level view for reference, archive data.

Topic #5: Approaches to prevention and control of bacterial vaccine-preventable diseases

(NCIRD/DBD/MVPDB).

5.1: Establish human challenge model of Bordetella pertussis infection to accelerate new pertussis vaccine development and licensure (NCIRD/DBD/MVPDB). CDC seeks to partner with scientists to accelerate development and licensure of next generation pertussis vaccines using a human challenge study approach.

CDC is particularly interested in understanding the pathobiology of pertussis disease, immunological and clinical response to B. pertussis exposure in persons who received acellular pertussis vaccines for the childhood series. Additionally, CDC is interested in identifying immune markers of protection against pertussis infection and disease that can be used in vaccine trials. The study will establish a reproducible and safe pertussis human challenge model to:

• Characterize time course and spectrum of clinical illness in adults primed with acellular vs whole-cell vaccines

• Determine rate of clearance of the bacteria from the nasopharynx once antibiotic treatment is started

• Evaluate the effect of antibiotic treatment on symptoms and infectivity

• Examine the inflammatory and immune response following infection and illness (innate and antigen-specific immunity)

• Evaluate infectivity of individuals with subclinical infections

• Collect biologic specimens to help with development of rapid diagnostic tests and criteria for diagnosis

5.2: Evaluate evolving transmission dynamics of circulating Bordetella pertussis under different vaccination strategies (NCIRD/DBD/MVPDB). Whooping cough (‘pertussis’) remains a public health challenge in many countries, including the US, even though vaccine coverage remains high. The US exclusively uses acellular pertussis (aP) vaccines composed of inactivated Bordetella pertussis immunogenic proteins, which replaced whole-cell (wP) preparations during the 1990s. Waning protection from aP vaccines has contributed to increased disease rates among vaccinated individuals and research to support development of future vaccines is needed. However, fundamental details about the transmission of

B. pertussis within populations, and the influence of vaccination, remain poorly understood. This request is for laboratory study of circulating B. pertussis to examine dynamics of transmission under varied vaccination strategies.

• Proposals should address one or more of the following needs:

• Examine potential differences in transmission among circulating genotypes of B. pertussis in animal models of pertussis. Applicable disease models should ideally compare transmission among aP and wP vaccinated as well as naïve and convalescent animals.

• Identify and characterize B. pertussis factors involved in transmission that might be suitable targets for intervention.

• Characterize the impact of transmission on disease resurgence using population genetics models of B. pertussis circulating in the United States. Computational, phylodynamic models should be equipped to handle the full set of available genomic data from recent B. pertussis clinical isolates. Additional epidemiologic parameters may also be included, where possible.

• Develop new evolutionary, and ideally epidemiologic, simulation-based models to test strategies targeting transmission for managing the spread of B. pertussis.

• Evaluate the potential contribution of asymptomatic infection (carriage) on the transmission of B.

pertussis.

5.3: Evaluate molecular characteristics of invasive isolates of H. influenzae, compared to carriage isolates from household contacts of patients and a control popoulation. Removed – Amendment 0001

5.4: Evaluate H. influenzae vaginal carriage among pregnant females. Removed – Amendment 0001

5.5: Evaluate cell-mediated immune response to natural pertussis infection and compare to immune response to pertussis vaccination. (NCIRD/DBD/MVPDB). CDC seeks to partner with scientists and laboratories to apply innovative methods to describe mechanisms of immune response to pertussis infection and vaccination to understand the pathobiology of natural infection and the protective immunity conferred by acellular and whole-cell pertussis vaccines. To that end, CDC is seeking to collaborate with partners with expertise and capacity to:

• Recruit adolescent and adult patients (including pregnant women) with laboratory confirmed pertussis and known pertussis vaccination history

• Recruit health adolescent and adults with known pertussis vaccination history

• Extract peripheral blood mononuclear cells (PBMCs)

• Collect plasma and isolate neutrophils

• Evaluate T cell response with appropriate assay

• Evaluate memory B cell response with appropriate assay

• Evaluate avidity and opsonophagocytosis with appropriate assays

Added – Amendment 0001

Topic #6: Developing information needed to advance Legionnaires’ disease prevention

(NCIRD/DBD/RDB). Legionnaires’ disease has been increasing in the United States, yet the vast majority of cases do not have evidence of direct link to outbreaks. CDC seeks research to add to our understanding of potential overlooked Legionella sources of exposure, with a particular focus on household water systems. We also seek innovative approaches for more rapid identification and effective elimination of

Legionella from building water systems. Moreover, CDC seeks state, academic, or other entities to better understand the underlying causes of the continued increase in reported Legionnaires’ disease cases in the

United States.

6.1: Development and evaluation of a rapid test to determine the presence of viable Legionella pneumophila within environmental samples (NCIRD/DBD/RDB).

Testing for Legionella bacteria in building water systems is time-consuming, laborious, and requires special skills and laboratory supplies. A rapid, culture-independent method of identifying live bacteria in water samples could dramatically improve response times in an outbreak setting. We are interested in the design and development of a rapid viability assay for Legionella bacteria present in environmental water samples.

6.2: Investigating possible genetic or other factors associated with increased survival of Legionella bacteria to heat, disinfectants, biocides, and other common remediation tools in water systems

(NCIRD/DBD/RDB).

Current strategies for remediation of water systems found to contain Legionella bacteria include heat shock and treatment with high levels of a biocide such as chlorine. Often, a single round of remediation is insufficient to completely eliminate the bacteria from the system. Little research exists on the possibility of resistance to these common response options. We are interested in gaining knowledge on possible genetic or other factors associated with increased survival of Legionella bacteria to heat, disinfectants, biocides, and other common remediation tools.

6.3: Enhancing whole genome sequencing data from clinical isolates of non-Lp1 bacteria to both increase our understanding of these less commonly identified strains and to augment domestic and international sequencing databases (NCIRD/DBD/RDB).

Approximately 90% of all reported cases of Legionnaires’ disease is caused by a single serogroup of bacteria, Legionella pneumophila Serogroup 1. This estimate may be affected by the fact that the most popular test for disease in the U.S. (the urine antigen test) is specific for this species and serogroup. We are interested in learning more about the diversity of non-Lp1 disease strains in the US. In particular we seek whole genome sequencing data from clinical isolates of non-Lp1 bacteria to both increase our understanding of these less commonly identified strains and to enhance domestic and international sequencing databases.

Topic #7: Surveillance for non-invasive pneumococcal pneumonia (NCIRD/DBD/RDB).

Given dramatic reductions in the burden of adult invasive pneumococcal infections through indirect effects of PCV use in children, non-invasive pneumococcal pneumonia is now the predominant syndrome among adults. Non-invasive pneumococcal pneumonia may be prevented by pneumococcal conjugate vaccine administration in children, or directly in adults. Higher-valency conjugate vaccines for adults are on the horizon and ACIP policy decisions will largely be driven by the expected impact of these vaccines on non-invasive pneumonia. There are no population-based surveillance systems for non-invasive pneumococcal pneumonia currently in the US to help establish disease incidence and guide future policy decisions.

7.1: Establish active pneumococcal urine antigen testing in adults 18 years of age or older with chest x-ray confirmed pneumonia in a defined catchment area (NCIRD/DB/ RDB).

To better understand the burden of non-invasive pneumococcal pneumonia, CDC seeks partners with innovative ideas to establish active pneumococcal urine antigen testing in adults 18 years of age or older with chest x-ray confirmed pneumonia in a defined catchment area. We are particularly interested in designs where population-based rates of urine positive, culture-negative pneumococcal pneumonia can be extrapolated. Ideally urine samples will be stored for serotype-specific testing at CDC.

Topic #8: Use Modeling and Forecasting Tools to Improve the U.S. Response to Seasonal and Pandemic

Influenza (NCIRD/ID)

8.1 Pandemic influenza simulation: Utilize innovative modeling techniques to create synthetic datasets that would be available during influenza pandemics (NCIRD/ID).

Since the 2013–14 influenza season, CDC and external researchers have collaborated to produce seasonal influenza forecasts through a project called FluSight [1]. While this collaboration has helped advance the science and usefulness of seasonal influenza forecasts, the process for generating forecasts during an emerging influenza pandemic is untested. Predicting pandemic activity and peak activity is essential for optimal pandemic responses such as pandemic vaccine production and distribution. Recently, synthetic datasets (defined as datasets generated by a disease model) were generated to simulate the 2014–2015

Ebola epidemic in Liberia [2]. These datasets were utilized to host a forecasting challenge that allowed development of new innovative approaches to forecasting and assessed how forecast performance was impacted by the epidemiological characteristics of the epidemic, data availability, or reporting quality.

Thus, the generation of synthetic datasets that simulate emerging influenza pandemics is a challenging and essential first step to stimulating new innovative methodology for a future pandemic by enabling a forecasting challenge with forecasting partners. CDC seeks an innovative solution to:

• Generate a synthetic pandemic influenza dataset for the United States using validated disease models and different pandemic assumptions about transmissibility and clinical severity while accounting for factors that will influence data availability, timeliness, and quality (e.g., care-seeking frequency and timing, influenza testing practices, data reporting timelines and backfill, etc.)

Topic #9: Address Critical Gaps in Knowledge of the Total Preventive Benefit of Currently Available

Influenza Vaccines (NCIRD/ID)

9.1: Clinical Research Networks to Improve Clinical Management of Hospitalized Influenza Patients

(NCIRD/ID)

CDC seeks to partner with Clinical Research Networks in the United States to assess clinical management of hospitalized patients of all ages with laboratory-confirmed influenza through prospective observational cohort studies that utilize a common protocol to collect and analyze pooled epidemiological (demographic, medical history, illness history, current season influenza vaccination) and clinical data for influenza patients admitted to general medical wards and intensive care units. Clinical outcomes may include disease progression requiring intensive care unit admission and advanced organ support, duration of advanced organ support, duration of hospitalization, in-patient mortality, disease progression or resolution utilizing clinical scoring systems (e.g. National Early Warning Score, Ordinal Scale). Current clinical management of hospitalized influenza patients is not standardized. This project will address the question of what is current clinical practice management of hospitalized patients with influenza? Data from this project can serve to describe baseline data on management of influenza complications to inform clinical trials of interventions [pharmacologic and non-pharmacologic (diagnostic assays, ventilator management)] with the goal of optimizing supportive clinical care. This effort will:

• Describe and assess data collection utilizing epidemiological and clinical data extraction from electronic health records versus utilizing a common case report form.

• Describe and assess influenza diagnostic testing in upper respiratory tract specimens in patients without respiratory failure, and in upper and lower respiratory tract specimens in patients with respiratory failure.

• Describe and assess antiviral treatment (specific drugs, timeliness of initiation, dosing, duration) and assess effectiveness (early versus late initiation versus no treatment) against clinical outcomes.

• Describe and assess management of complications, including pulmonary (community-acquired pneumonia and other pulmonary complications), extrapulmonary complications, multi-organ failure, and sepsis.

• Describe and assess advanced organ support in critically ill patients (non-invasive, invasive mechanical ventilation, ECMO, prone positioning, renal replacement therapy, vasopressors).

• Describe and assess use of serum biomarkers (procalcitonin, C-reactive protein) at admission to distinguish influenza virus infection alone from influenza with community-acquired invasive bacterial infection; and assess serial plasma and serum specimens for biomarkers to correlate with interventions and clinical outcomes.

• Describe and assess oxygen delivery (high flow nasal canula, positive pressure non-invasive ventilation, invasive mechanical ventilation.

• Describe and assess diagnostic testing for invasive co-infections, including bacterial or fungal co-infections at admission; and nosocomial infections, especially in critically ill patients (ventilator-associated pneumonia with bacterial or fungal infections), and antimicrobial therapy regimens

(specific antimicrobials, dosing, and duration of treatment).

• Describe and assess use of adjunctive therapies, including drugs with immunodulating activity

[use of corticosteroids and dosing (low, moderate, high-dose), macrolide antibiotics].

• Describe and assess fluid management – conservative versus liberal fluid management – in critically ill patients.

• Describe and assess adherence to the American Thoracic Society - Infectious Diseases Society of

America Guidelines for Adults with Community-Acquired Pneumonia, and the Infectious

Diseases Society of America Influenza Clinical Practice Guidelines.

9.2: Innovative methods to evaluate the role of influenza vaccines in attenuating severe disease in adults

NCIRD/ID).

CDC seeks to improve the overall preventive benefit of the U.S.’s influenza vaccination program and improve pandemic preparedness, specifically through understanding the role of vaccines in preventing critically severe illness. Influenza vaccines provide moderate protection against illness requiring outpatient medical visits and inpatient care. A limited body of evidence also suggests that a gradient in protection may exist wherein influenza vaccines may halt or attenuate the progression of illness, and thus limit severe post-infectious disease when influenza infection is not prevented. However, evidence on disease attenuation from influenza vaccines has been mixed in the inpatient settings largely due to challenges and drawbacks related to study design, population, methods, and execution. Addressing these challenges in the inpatient setting enhances our ability to quantify the benefits of influenza vaccines.

Through previous collaborations and research efforts, CDC has developed study protocols and refined influenza severity scores for assessing vaccine attenuation through observational designs. However, these study designs and severity scores need refinement and validation in additional seasons with different viruses and changing vaccination dynamics. To leverage these experiences and address critical knowledge gaps regarding the disease attenuating mechanisms and properties of currently available seasonal influenza vaccines in the inpatient setting. CDC seeks a partner who can apply innovative and efficient methods to:

• Establish a new network of ICUs (or build upon an existing network) in the U.S. that would refine and apply a common protocol and case-definition to facilitate the evaluation of influenza vaccine effectiveness against disease progression. Within this network, the partner should apply innovative and efficient solutions to:

• Identify a comprehensive set of clinical and laboratory parameters relevant for refining and validating an influenza-specific physiologic severity score that can be applied for evaluating influenza vaccine effectiveness against disease progression

• Create a repository for this information and implement appropriate analytic methods to apply and interpret this information.

• Develop and implement a strategy for collecting blood and respiratory research specimens from a subset of vaccinated and unvaccinated patients to facilitate the evaluation of susceptibility to severe infection and mechanisms of disease attenuation (e.g., antibody kinetics, correlates of protection, microbiome differences, proteomics).

• Develop and implement a methodology to examine patients in the ICU setting and a subset of patients in non-ICU inpatient setting to capture the full spectrum of inpatient disease severity.

• Apply innovative methods to assess and interpret vaccine effects against range of severe disease by factors such as age, time since vaccination, prior vaccination, vaccine type, and virus-type

• Integrate standard and novel methods for identifying sub-phenotypes in critically ill patients (e.g., sepsis, acute respiratory distress syndrome) to reduce the heterogeneity in influenza severity syndromes and advance the evaluation of vaccine effectiveness against disease progression.

9.3 Innovative methods to improve estimates of influenza vaccine effectiveness for different influenza vaccine types. (NCIRD/ID)

The variety of licensed influenza vaccine products available in the US has increased substantially in recent years. Yet, there is limited information on the relative effectiveness of different vaccine types

(e.g., high-dose influenza vaccine, MF59-adjuvanted vaccine, cell-based manufactured vaccine) in preventing medical care associated with laboratory-confirmed influenza…