Appendix D ID NCHHSTP STD Laboratory Innovations and Continuation of AR Projects.pdf

Division of Laboratory Systems

Excellent Laboratories, Outstanding Health

CENTERS FOR DISEASE CONTROL AND PREVENTION

DIVISION OF LABORATORY SYSTEMS

CENTERS FOR DISEASE CONTROL AND PREVENTION

DIVISION OF LABORATORY SYSTEMS

Excellent Laboratories, Outstanding Health

CDC-RFA-OE20-20010101SUPP20: Enhancing Public Health Laboratory Capabilities and Increasing Capacity

Supplemental Project Proposal Appendix D: Infectious Diseases - NCHHSTP

Appendix D: Infectious Diseases Focus Area Name Infectious Diseases

Focus Area Contact Information Brandi Limbago, bbl7@cdc.gov Serena Carroll, awx6@cdc.gov Michelle Owens, smo2@cdc.gov

1. General Information

Project Name: ID_STD: STD Laboratory Innovations and Continuation of AR Projects

Project Activity Contact Information: Technical Monitor, Kevin O’Connor (kpo1)

Approximate Amount of Supplemental Funding Available:

$500,000.

2. Project Description

The activities and projects in this proposal are built around innovative STD Laboratory methods for multiple pathogens such as direct pathogen direction, genetic detection methods for multiple pathogens together, enhanced training opportunities for STD Laboratory personnel, and CDC antibiotic resistance detection and response activities centered in DSTDP’s ‘Improving Gonorrhea (GC) Resistance Testing Methods’ plan. The approach is to roll out innovative technology for STD pathogen detection, to evaluate laboratory methods to increase viable GC isolate recovery rates and to develop methods to detect resistant GC or other STDs (T.

pallidum, Chlamydia -LGV, Mycoplasma genitalium) by PCR from swab specimens without the need for culture. Obtaining a viable isolate is critical for current gonorrhea antibiotic resistance testing methods, and also for full genetic characterization of T. pallidum and LGV strains.

Historically antibiotic resistance detection for gonorrhea was reliant on culturing the organism;

however, in the current era laboratory culture capacity for GC is quite rare and identification of resistant organisms is increasing difficult. Because gonorrhea prevalence is increasing, and antibiotic resistance continues to evolve, robust strategies for antibiotic resistance detection are essential.

Specimens from women and from extragenital sites often have poorer laboratory growth outcomes than urogenital specimens from men. Viability is often lost along the chain from specimen collection, transport to laboratory, and laboratory growth confirmation. Alternatively, genetic detection of resistance genes directly from swab specimens is possible, but currently not implemented due to lack of validated methods. We propose to work with existing AR Lab Network specimen submitters/ public health laboratories to support complementary strategies to enhance both culture-based and molecular detection of resistant gonorrhea strains.

mailto:bbl7@cdc.gov mailto:awx6@cdc.gov mailto:smo2@cdc.gov

APHL will be funded to convene didactic workshops on STD testing, the antibiotic resistance lab network, and advanced molecular detection (AMD). They will host webinars on infectious disease testing topics geared for public health and clinical laboratory audiences. Additional activities will include GC culture and eTest Training, PCR roll-out and evaluation, specimen acquisition for assay validation and verification, real world GC transport evaluation, and travel and other training activities in support of these efforts.

i. Purpose

This proposal builds on our funded efforts with APHL and is part of STD ‘Improving gonorrhea resistance testing methods’ activities. These supplemental activities are for a total of $500,000 and includes:

• Project 1. GC culture and eTest Training (on site at CDC. Proposed funding - $98,000

• Project 2. PCR roll-out and evaluation (for STI such as Treponema pallidum [syphilis], for Genital Ulcer Disease detection [T. pallidum, HSV, and H. ducreyi, potentially additional pathogens], Chlamydia trachomatis – LGV serovars, and if applicable, GC resistance genes, e.g., penA. Proposed funding - $75,000

• Project 3. Specimen acquisition for STD (LGV, syphilis, M. gen) and associated AMR specimen repository (left-over specimens for assay validation and verification proposed funding - $50,000)

• Project 4. “Real-world” GC transport media evaluation. Proposed funding $277,000;

includes study design and protocol development.

Justification: Funding of activities will allow the Roll-out of mostly lab-developed innovative detection methods for STI detection, and continuation of

Gonococcal Antibiotic Resistance Projects.

There are currently no FDA-cleared genetic direct detection tests for T.

pallidum (syphilis) detection, for H. ducreyi (chancroid) detection, or for

Chlamydia trachomatis LGV detection. In addition, there is no genetic resistance detection test for the emerging pathogen Mycoplasma genitalium, or for Neisseria gonorrhoeae. CDC laboratorians have successfully developed laboratory tests for these organisms and/ or associated resistance genes. One part of this proposal is to roll out and implement some of these assays in public health laboratories. This will be a continuation of previous efforts and collaborations, where demonstration projects have yielded successes. In addition, CDC has declared that antibiotic resistance (AR) is one of the biggest public health threats of our time. The threat of AR is complex and far reaching.

CDC includes gonorrhea (GC) as one of its five urgent AR threats. GC has progressively developed resistance to numerous antibiotics over the last several decades, beginning with penicillin. GC can cause serious health problems including ectopic pregnancy, pelvic inflammatory disease, and infertility. GC is easily transmitted through sexual contact and rates have been rising steadily over the past decade. Currently there are over 550,000 reported cases in the United States annually. GC can effectively be treated with cephalosporins and azithromycin to cure infections, prevent transmission, and avoid further complications. However, the specter of cephalosporin-resistant

GC is looming as numerous studies have documented decreased susceptibility.

The emergence of untreatable GC would be a tragedy of immense proportions and should be avoided if at all possible. This proposal takes several steps to assist public health labs more rapidly detect and classify antibiotic strains of

GC. Improved culture capacity coupled with the use of etests for selected antibiotics could allow laboratories to facilitate a more rapid response to AR

GC outbreaks. Better understanding of resistance and/or molecular markers could also help ensure infected individuals receive the most appropriate therapy. CDC has learned through multiple rounds of resistance development and changed treatment recommendations, that switching recommended therapies when critical thresholds are reached can reduce transmission of resistant strains and ensure effective treatment of patients. This work will enhance surveillance activities that inform treatment recommendations.

These funds will support development of tools and strategies to enhance detection of resistant strains and better understand the nature of the resistance. Funds will also support dissemination of standards and practices in public health labs.

ii. Identification of need (please state who identified the need APHL or CDC)

CDC identified AR GC as a priority public health threat in 2013 and since that time DSTDP has worked with APHL and other partners on several projects related to detection of AR strains, dissemination of culture and other detection technologies, and antibiotic resistance testing including etests. CDC broadly developed the strategies proposed here and worked with APHL to refine activities so that implementation would be feasible and the likelihood of success would be increased. In addition, syphilis rates are rising in the US.

Currently, syphilis diagnosis is based on serology and sequential antibody test combinations. Having a direct detection test for the pathogen at earlier disease stages and before antibodies develop could be an advance and could lead to faster detection and transmission prevention. Both APHL and CDC are aware of the need for better syphilis testing and have previously collaborated extensively on this issue. Lastly, Chlamydia trachomatis is the most commonly reported infection to CDC in the US. It is currently unknown how many CT infections are due to more invasive LGV strains. Introducing a lab developed

LGV test will be beneficial for detection of such strains and will allow more appropriate interventions. APHL and CDC have previously identified this need and have collaborated on it by procuring specimens for the development of a test at CDC.

iii. New or expanded project: This is an expanded project as it will advance and enhance the capabilities, skills, and capacity of public health laboratory staff which would result in improved gonorrhea resistance testing, effectiveness of treatments, and CDC’s ability to respond to outbreaks of AR GC.

Activities below are an expansion of current support provided through the Enhancing Public Health Laboratory Capabilities and Increasing Capacity Cooperative Agreement (CDC-RFA- OE20-2001). APHL will support these testing and diagnostic needs as follow:

• Project 1. GC culture and eTest Training (on site at CDC proposed funding - $98,000) o APHL will convene a working group of SMEs to draft a lab training curriculum on specimen collection, GC culture, shipping methodologies and etesting. A series of culture and etest workshops will be conducted to train laboratorians in PH labs intending to enhance their AR GC culturing and testing capacity.

• Project 2. PCR roll-out and evaluation (for STI and if applicable, resistance genes, e.g., penA) proposed funding - $75,000) o APHL will identify PH lab candidate sites to partner in a PCR roll-out and evaluation. In this role, APHL will purchase equipment and materials required for

PCR diagnostics and assessment of outcomes.

• Project 3. Specimen acquisition for STD and associated AMR specimen repository (left-over specimens for assay validation and verification proposed funding - $50,000) o APHL will identify partner labs to collect and retain STD specimens in a repository that will support improved diagnostic capacity and quality (e.g.

providing validation panels for laboratory-developed tests).

• Project 4. “Real-world” GC transport media evaluation (proposed funding $277,000;

includes study design and protocol development).

o APHL will purchase inTrays, incubators, media and other materials required for real-world implementation of GC culturing, incubation, and shipping. At least three partner sites (including STD clinics and associated laboratories) will participate and will collaborate on an evaluation of the approach.

3. Outcomes

Activities in this project should achieve or contribute to the following proximal outcomes:

• PO-1. Improved collaboration and communication across public health laboratories and other stakeholders.

• PO-4. Improved awareness of new tools and resources for public health laboratories and stakeholders.

• PO-5. Improved awareness and understanding of public health laboratory workforce development needs and opportunities.

• PO-7. Enhanced technical and non-technical knowledge, skills, and abilities among public health laboratory professionals in diverse settings.

• PO-8. Improved understanding of data-related challenges and data-informatics solutions among laboratory professionals and stakeholders

Activities in this project should achieve or contribute to the following intermediate outcomes:

• IO-1. Established communities of practice and other collaborative relationships among and between laboratories and other stakeholders.

• IO-3. Improved competence and engagement of public health laboratory workforce.

• IO-4. Enhanced practices, methods, technical capabilities, and infrastructure within the public health laboratory system.

• IO-5. Improved data exchange and interoperability among public health laboratories and their partners.

• IO-6. Improved public health laboratory detection, surveillance, and response.

Activities in this project should contribute to the following long-term outcome:

Improved effectiveness of public health laboratories, individually and as components of a national system

4. Strategies and Activities

List specific strategies, activities, and process measures

Strategy/Activity Process Measures

1. S2.2 Collaborate and build relationships among laboratory professionals and other stakeholders in public health, healthcare, and beyond.

• Increase % of PH labs with

GC culture and etest capabilities and with capacity to test directly for T.

pallidum, LGV, and other

STIs

2. S2.3 Facilitate information exchange and dissemination among practitioners and other stakeholders.

• Increase % of PH labs that follow CDC recommendations on GC resistance testing

• Creation of standardized metrics of AR GC surveillance

3. S2.4 Educate the public and other stakeholders about the role of public health laboratories.

• Increase the percent of HC providers who submit GC cultures to PH labs for resistance testing

S3.1 Identify training and workforce development needs among laboratory professionals in diverse settings

• # courses offered and attendees at lab trainings on

STD diagnostics

S3.3 Facilitate the development and delivery of training and workforce development resources.

• Development of a curriculum for lab training on STD diagnostics

S3.3 Facilitate the development and delivery of training and workforce development resources.

• Identification, classification, and dissemination of standardized protocols for

STI detection and molecular markers of GC or Mgen resistance

S4.1 Develop and implement informatics-related solutions and standards to improve data exchange and interoperability.

N/A

S4.2 Identify and address systems to improve the practice of laboratory quality and safety in public health laboratories.

• Creation of GC and syphilis specimen banks at CDC to support enhanced diagnostics in PH labs

S4.3 Identify and address emerging methodological and process improvements in public health laboratories.

• # courses offered and laboratorians trained on GC culture and etest approaches and on implementation and validation of lab-developed tests for pathogen detection

S4.4 Provide technical assistance to state and local public health laboratories to support improvements in public health outcomes.

• # PH labs who access CDC specimen banks to enhance their diagnostic capacity

S4.5 Identify and address gaps in laboratory infrastructure and capability to prepare and respond to public health threats.

• # PH labs conducting culture-based GC etesting

• # of PH labs implementing and validating lab-developed tests for pathogen detection

5. Budget

CELS/DLS project officers will provide budget spreadsheet for APHL to complete for requested funds by object class category

By submitting this project plan, I certify that my CIO currently does not maintain a comparable NOFO for similar activities and the proposed use of funds is consistent with the appropriation.

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T e c h n i c a l M o n i t o r S i g n a t u r e

S i g n e d b y : P I V

Please note: APHL is expected to collaborate with their CDC point of contact and/or technical monitor for this project to develop realistic measurable process objectives. In response to this proposal, APHL should provide a detailed work plan with: Outcomes, outcome measures, strategies/activities, and process measures.