Attachment 1 - Statement of Work.pdf

STATEMENT OF WORK

Syphilis samples for Treponema pallidum strain characterization, test development and antimicrobial resistance monitoring

C.1 Background and Need

Syphilis is an ongoing public health concern among gay, bisexual and other men who have sex with men (GBMSM) in the United States. Since 2001, disease rates in the US have continued to rise, especially among GBMSM, despite effective first line treatment with penicillin. More recently, rates have increased in men who have sex with women only. Rates of congenital syphilis have reached a 20-year high with 918 cases reported in 2017 alone. Furthermore, two ocular syphilis clusters were reported in Seattle and San Francisco in 2015 and since then there have been reports of ocular syphilis cases in 15 states. From a public health standpoint, syphilis is one of the most important bacterial causes of genital ulcer disease (GUD), which may facilitate the acquisition and transmission of other sexually transmitted infections (STIs), including herpes simplex virus (HSV) and human immunodeficiency virus (HIV), and causes significant health complications in adults and infants if untreated.

Misdiagnosis and delayed treatment of the highly infectious primary and secondary syphilis lesions contribute significantly to ongoing transmission, and ultimately, the epidemic burden of this infection. Current clinical practice relies mainly on serological testing with limited use of darkfield microscopy (DF) for syphilis diagnosis. Polymerase chain reaction (PCR) can be very useful for diagnosis during early primary syphilis when lesions appear, but serological tests can be negative. However, PCR use for syphilis is limited in the US since there are no US Food and Drug Administration (FDA)-cleared nucleic acid amplification tests (NAATs). A recent study showed a PCR sensitivity of 83.9% in maculopapular skin lesion specimens of secondary syphilis collected by superficial scraping of the lesions followed by swabbing, suggesting that the low sensitivity reported in other studies may have been due to inadequate sampling.

Although serology remains the mainstay for the laboratory diagnosis of all stages of syphilis there are research needs to improve testing options such as comparison of automated versus non-automated non-treponemal tests; comparison of the performance of automated immunoassays by stage or comparing their performance versus manual treponemal tests; and performance of the traditional and reverse algorithms.

Azithromycin has been shown to be as effective as penicillin for treating early syphilis;

however, azithromycin-resistant T. pallidum strains have been reported in multiple areas in the US and consequently, it is no longer recommended as a first-line treatment option.

Two mutations in the 23S rRNA genes are associated with azithromycin resistance. A surveillance study done in 2007, in the US, showed an overall prevalence of the A2058G mutation in 53% of genital lesion swabs collected in 11 STD/HIV clinics. A subsequent study using a subset of these samples, found the A2059G mutation in 13.2% of samples.

A significant increase in the prevalence of T. pallidum resistant strains has been reported in San Francisco (21.8% to 67.7%) and Seattle (13% to 71.9%) over an 8- and 9-year period, respectively. The current prevalence of azithromycin resistant strains in the US is not known.

Shortages of bicillin have occurred in the past requiring the use of alternatives such as doxycycline for the treatment of syphilis. There have been no reports of syphilis treatment failure associated with the tetracycline class of antibiotics and surveillance studies in four countries have not detected mutations associated with tetracycline resistance in T. pallidum. It is hypothesized that resistance might arise from point mutations in the 16S rRNA gene at nucleotide positions 965–968 (AGA) or 1058 (G) as shown in H. pylori and E.coli. There is no available research data on the impact of doxycycline use on the emergence of tetracycline-resistant T. pallidum strains in the US.

C.2 Project Objective

To collect syphilis specimens to start a repository for use in development/evaluation of serological and molecular diagnostic tests, and molecular surveillance of T. pallidum.

CDC requires a contractor to collect paired swab and serum samples in clinical settings from participants with darkfield-positive lesions, moist lesions suspicious of primary and secondary syphilis (genital or anal ulcers, mucous patches, condyloma lata), or maculopapular. A patient history form will also need to be completed to ensure accurate clinical staging of syphilis. All lesion swabs and sera shall be provided to the Centers for Disease Control and Prevention (CDC), Deputy Director for Infectious Diseases (DDID), National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP), Division of STD Prevention (DSTDP), Laboratory Reference and Research Branch

(LRRB).

C.3 Scope of Work

This is a research activity which aims to collect specimens from individuals who present to STD/HIV clinics, local health departments, and other health care facilities with symptoms related to syphilis diagnosis and are well-characterized clinically. The contractor (medical personnel) will engage in routine collection of lesion swabs and sera in the context of a standard clinical encounter with patients directed for STD/HIV testing.

The contractor will store the specimens and complete a case history form by abstracting information from existing patient records. The specimens will then be shipped to CDC.

Participants in this study will not be asked specific study-related questions during the routine clinical care and no identifiable information such as name, address, or date of birth will be collected. Participants will be asked to sign a consent form and clinic staff will inform them that their names will not be disclosed and that the data obtained from the research may be combined and published in papers or reports. In addition, patients will be informed that details from an individual patient history form cannot be linked to a specific participant. None of the information collected will be shared with anyone outside the research team. The abstracted clinical data will help to determine if serology results are altered by HIV infection or pregnancy, and if there are any associations between T.

pallidum strain type and resistance markers, HIV status, or sexual behavior, etc. Results from this research activity will not be used for patient management.

The contractor must have access to clinics, local health departments, or other health care facilities that perform darkfield microscopy testing, and have clinicians who are experts in the management of ulcerative STDs with experience in collecting genital lesion swabs.

A minimum of twenty (20), and no more than forty (40) paired lesion swab and serum specimens meeting the criteria in Task 6 shall be sent to the CDC. The CDC will make payment at the firm-fixed-price per unit specified in the purchase order for each shipment meeting the criteria and containing all required documentation that is received and accepted.

An acceptable shipment is comprised of the following items:

1. Paired lesion swabs (QTY 2)

2. Serum Sample (QTY 1)

3. Signed Patient Consent Form

4. Evidence of proper specimen storage

5. Completed Patient History Form

6. Printed line list of swab and serum specimens with specimen identifications

C.4 Technical

The contractor shall provide all labor, expertise, and perform all services required to carry out the work under this contract.

Task 1: Start Up Meeting

The contractor shall arrange and conduct an initial meeting (by teleconference) with the COR and other relevant staff within 2 weeks of the start of the period of performance. The purpose of the meeting will be to review the scope of work and delivery schedule for tasks, to delineate roles and responsibilities, and to establish communication protocols. Each task and deliverable will be reviewed.

The contractor shall submit an agenda for the above meeting within 1 week of the start of the period of performance of the contract.

The contractor shall provide minutes of the meeting within 1 week after the meeting.

Task 2: Maintain Communication with the Project Officer

The contractor shall coordinate with the COR for all project related communications.

The contractor shall maintain regular communications with the CDC Science Officer and COR involved with the project.

The contractor shall participate in at least one conference call per quarter with CDC personnel. Additional calls will be scheduled as needed. The contractor shall provide an agenda and meeting minutes for each call. All conference calls shall be scheduled and administered by the contractor.

The contractor shall respond to all emails and telephone communications from the CDC Science Officer within 3 working days.

Task 3: IRB Approval

IRB approval is required for prospective collection of lesions swabs and serum and the contractor will complete institutional review board (IRB) applications and ensure that the project is reviewed and approved by the appropriate IRBs. The Contractor shall prepare the packages including all forms and attachments for CDC Science Officer approval as needed. The Contractor shall submit the IRB package to their IRB and ensure that all clinical sites involved in the study apply for and receive IRB approval.

Copies of IRB approvals from the Contractor and all clinical sites shall be provided to the CDC Project Officer.

CDC Project Officer will provide copies of the patient history and consent forms for the contractor to obtain IRB approval.

Keys enabling linkage of personal identifying information (PII) to private information or specimens shall not be released to the CDC.

The contractor shall attest that the release of data and the purposes of the planned research do not contradict the terms of consent under which the information or specimens were collected.

Task 4: Quarterly Progress Reports

By the 10th calendar day following the 3 months being reported, the contractor shall prepare and submit a quarterly progress report containing the current status of work.

The report shall contain, at a minimum, the current progress on each of the requirements set forth in the SOW, problems encountered during the month, unforeseen delays in collection and shipment of specimens, solutions implemented, planned activity for the upcoming month and any other information requested by the CDC Science Officer.

If it is anticipated that the minimum of 20 paired lesion swab and serum specimens cannot be obtained during the collection period, the contractor must explain the lack of specimens and provide a mitigation plan for future specimen collection in the quarterly progress report before the first day of the 6th month of the project.

Task 5: Collection of Specimens

Upon submission of IRB documents by the contractor for approval at CDC, CDC will ship swab collection kits, serum tubes, and barcode labels (refer to paragraph C.5 below).

The contractor shall collect paired lesion swabs and serum specimens from men and women with moist lesions suspicious of primary or secondary syphilis (genital or anal ulcers, mucous patches, or condyloma lata), or maculopapular rash. Lesions swabs from participants with maculopapular rash or mucous patches shall be collected if both treponemal and non-treponemal serological tests are reactive. A flowchart for moist lesion swab and serum specimen collection, diagnostic testing and storage is shown in (Appendix 1). Serum samples collected for this study shall be aliquoted and stored frozen if routine serology testing for patients will be delayed or done at another facility. Maculopapular rash should be lightly abraded before swabbing the lesion.

The Contractor is responsible for all coordination with clinics, health departments or other health care facilities involved in collection, testing and storage of specimens.

If serology is not performed the same day at the clinic or if sera are sent to the Public Health Laboratory (PHL) for testing then, lesion swabs and sera shall be stored as indicated below until serology results are available.

Swabs should be stored in a -80 oC freezer. If a -80 oC freezer is not available then swabs and serum can be stored at -20 oC.

Task 6: Qualifying Sample Criteria and Shipment

Specimens shipped to CDC must meet the following criteria:

o Darkfield Microscopy (DF)-positive primary or secondary moist syphilitic lesions (genital or anal ulcers, or condyloma lata);

o DF-negative lesions AND reactive treponemal (e.g., T. pallidum particle agglutination (TPPA)/ enzyme immunoassay (EIA) AND non-treponemal tests (rapid plasma reagin [RPR]/ Venereal Disease Research Laboratory [VDRL]) with no history of syphilis OR non-treponemal test (RPR/ VDRL) with titer ≥4-fold increase above most recent titer in patient with history of syphilis, OR STAT RPR reactive with no history of syphilis, OR STAT RPR reactive with titer ≥4-fold increase above most recent titer in patient with history of syphilis OR STAT RPR non-reactive with suspected primary syphilis, OR non-reactive treponemal and non-treponemal tests with suspected primary syphilis;

o DF not performed in the clinic but presence of suspicious lesions AND reactive treponemal (e.g., TPPA/ EIA) and non-treponemal tests (RPR/ VDRL) with no history of syphilis OR non-treponemal test (RPR/VDRL) with titer ≥4-fold increase above most recent titer in patient with history of syphilis OR STAT RPR reactive with no history of syphilis, OR STAT RPR reactive with titer ≥4-fold increase above most recent titer in patient with history of syphilis, OR STAT RPR non-reactive but primary syphilis suspected, OR non-reactive treponemal and non-treponemal tests but primary syphilis suspected.

o Serology positive (reactive treponemal AND non-treponemal tests) and lesions suspicious of secondary syphilis (maculopapular rash or mucous patches)

Contractor shall notify the CDC Science Officer via email at least one day prior to shipment.

Contractor shall provide an electronic copy of the line list by email at least 1 day prior to shipment.

Patients who have received penicillin, ceftriaxone or another beta-lactam antibiotic in the last 30 days will be excluded from the study.

Lesion specimens will not be accepted if not accompanied by a completed patient history form, including serology results.

Contractor shall include electronic copies of patient history forms, without PII, for all specimens at least 1 day prior to shipment.

No patient-level identifiers shall accompany specimens sent to CDC.

Shipping costs for the collected specimens will be covered by CDC (refer to paragraph C.5). The provided FedEx account number shall only be used to ship collected specimens to CDC and not for any other purpose.

Contractor shall include a printed line list of swab and serum specimens with each shipment.

All specimens should be shipped to CDC early in the week (i.e., Monday or Tuesday) to avoid specimens being left unattended over the weekend.

Contractor shall ship all specimens frozen on dry ice in accordance with International Air Transport Association (IATA) guidance. See (http://www.iata.org/whatwedo/cargo/dgr/Pages/download.aspx) and CDC Shipping and Packing guidance (http://www.cdc.gov/laboratory/specimen-submission/shipping-packing.html) for additional information.

Specimens shall be batched and shipped quarterly.

Task 7: Final Report

At the conclusion of the collection period, the contractor shall provide a line list of all specimens shipped under this agreement in electronic spreadsheet format including all completed patient history forms. The report shall include lessons learned, and recommendations for future efforts to implement syphilis specimen collection.

C.5 Government Furnished Property

CDC will provide swab collection kits, serum tubes, barcode labels, and a FedEx shipping account number to the contractor for the purposes of all shipments of specimens to CDC under this contract. The provision of the CDC’s FedEx account information shall be for the purposes of this contract alone and shall not be used by the contractor for any other contract, even other contracts with CDC. Specifics on shipping specimens have been outlined in Task 6.

C.6 Deliverables

Task Number

Deliverable Quantity/Format Recipient Frequency/Due Date

Task 1 Initial planning meeting agenda and minutes

1 copy COR Agenda within 1 week and teleconference within 2 weeks of contract award.

Minutes within 1 week of meeting.

Task 2 Agenda and minutes for one conference call per quarter, response to emails and telephone communications

4, quarterly, plus as needed

COR Agenda at least one day before the conference call.

Responses to emails and calls within 3 days of event.

Task 3 IRB approval letter from all participating sites

1 copy COR Within 3 months of the start of the period of performance

Task 4 Current status of work and summary of specimen collection and shipments

Mitigation Plan by month 6 if contractor ascertains that the minimum of 20 specimens cannot be collected or delivered

4, every 3 months beginning 3 months from start of contract

1 copy

COR

COR

10th day following the 3 months being reported

Within 1 week following the first 6 months of contract performance

Task 5 Minimum of 20 lesion swabs in transport medium (2 swabs per participant)

Minimum of 20 Sera in cryotubes

Number will vary;

Batched and shipped quarterly

COR First shipment of specimens due by the end of the 4th month of the period of performance, remaining shipments quarterly thereafter

Task 6 With each shipment, contractor shall include a printed copy of the line list of specimens and electronic copies of the patient history forms

No patient-level identifiers shall accompany isolates sent to CDC

Varies, quarterly COR All shipments must arrive at CDC by the end of the period of performance

Task 7 At the conclusion of the collection period, the contractor shall provide a report, which includes a line list of all specimens shipped under this

1 Final Project Report

COR No later than the final day of the period of performance

C.7 Period of Performance

August 1, 2020 through July 31, 2022.

agreement in electronic spreadsheet format including all completed patient history forms

Report shall include lessons learned, and recommendations for future efforts to implement syphilis specimen collection