Summary
The Association of Public Health Laboratories (APHL), in cooperation with the US Centers for Disease Control and Prevention (CDC) Division of Tuberculosis Elimination (DTBE), is seeking to award one-time funding for up to 20 state or local public health laboratories (PHLs) for the purpose of enhancing capacity for drug susceptibility testing (DST) of Mycobacterium tuberculosis (MTB), specifically with respect to fluoroquinolones (FQ) and rifampin (RIF). Funding will be awarded via a contract with APHL.
Eligibility
All state or local US public health laboratories that currently perform first-line pDST for MTB are eligible to apply for the one-time funding. Potential application scenarios include:
Option 1: Public health laboratories that currently perform pDST for rifampin using 7H10 Middlebrook and/or MGIT and would like to evaluate the updated WHO CC of 0.5 mg/L.
Option 2: Public health laboratories that currently perform first-line DST for MTB and would like to evaluate a FQ phenotypic or molecular susceptibility testing method(s) for MTB.
Note: Laboratories may apply for both Option 1 and Option 2, but each option will be evaluated separately.
Anticipated RFP Schedule
August
29,
2023 RFP Issued
September
6,
2023 Informational Teleconference (register here)
September 15,
2023 Required Letter of Intent Due to APHL (see below)
October
13,
2023 RFP Responses Due
October
27,
2023 Proposal
Review
Completed
November
1-3,
2023 Follow-Up
Interviews and
Updated
Proposals
Due (if needed)
November
10,
2023 Final
Review
Completed and
Awardees
Selected
December
1,
2023 Estimated
Contract
Start
Date
APHL will communicate any modification to this
anticipated schedule on APHL’s procurement website (www.aphl.org/rfp) and via an email blast to public health laboratories.
Final Response
APHL must receive complete responses by
11:59 pm EDT on
October 13, 2023. Please see
Proposal-Required Submissions section for items that must
be included in the completed proposal. Applicants may send proposals via email to
Sarah.buss@aphl.org
with a copy to
infectious.diseases@aphl.org.
APHL will send an email acknowledging the receipt of your application; if you do not receive an acknowledgement within
two business days, please email the RFP point of contact above to confirm receipt.
RFP Materials
APHL will post all RFP-related documents, current schedule information and answers to all submitted questions and clarifications on APHL's procurement site, The official RFP document will provide detailed information in regards to this request, please read it in its entirety.
Questions and Answers
Where can I find the RFP application?
A:The
official RFP documentcontains the questions that will need to be addressed in a complete application, beginning on page 8.
For evaluation of fluoroquinolone phenotypic testing does it matter which method of testing is used?
A:We are not being prescriptive with which testing method is used. You are free to propose evaluation of the methods that make the most sense for your laboratory.
For option 2, can you evaluate both phenotypic and molecular methods if you are currently only doing growth-based (phenotypic) testing?
A:Yes, as long as you are currently performing some kind of first-line susceptibility testing.
Is there any support for the protocols?
A:For the rifampin work, the following reference offers guidance:
Technical Report on critical concentrations for drug susceptibility testing of isoniazid and the rifamycins (rifampicin, rifabutin and rifapentine)
A:For the fluoroquinolone work, the following references offer guidance:
Technical Report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis This is the comprehensive document that was mentioned in the informational call.
A:CLSI’s m24, Susceptibility Testing of Mycobacteria, Nocardia spp. and Other Aerobic Actinomycetes and M24S, Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp. and Other Aerobic Actinomycetes are also good resources but are available to purchase and cannot be shared here. (On 7H10, CLSI recommends testing levofloxacin at 1.0 µg/mL, and moxifloxacin at 0.5 µg/mL. Using Mycobacteria Growth Indicator tubes (MGIT), CLSI recommends testing levofloxacin at 1.5 µg/mL, and moxifloxacin at 0.25 µg/mL. CLSI also recommends testing of moxifloxacin on 7H11 at 0.5 µg/mL.)
A:Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance
A:Currently, eleven public health laboratories report performing some kind of fluoroquinolone susceptibility testing. Six of these laboratories report utilization of agar proportion to test ofloxacin, levofloxacin and / or moxifloxacin; four laboratories report utilization of broth dilution to test ofloxacin, levofloxacin, ciprofloxacin and / or moxifloxacin and one laboratory reports utilization of an automated broth culture system to test moxifloxacin. At this time, we do not know if these laboratories are willing to discuss their protocols with applicants. Please email sarah.buss@aphl.org and infectious.disease@aphl.org with specific requests and APHL will contact the appropriate laboratory on your behalf.
Is there a recommendation for which moxifloxacin concentrations to use for MGIT-based testing? 0.25 mg/L is the World Health Organization (WHO) critical concentration, should we be considering testing at a higher concentration if resistant to 0.25 mg/L?
A:If you see fluoroquinolone resistance at the WHO critical concentration for moxifloxacin, you should consider reflexive testing at higher concentrations. Therefore, you can propose to evaluate a range of concentrations.
A:The CLSI M24S, Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp. and Other Aerobic Actinomycetes is a good reference for this topic.
Will there be isolates available to us for these evaluations?
A:Yes. Twenty isolates, characterized by the CDC using whole genome sequencing and MIC testing, will be available by request once contracts are in place. APHL will notify awardees of the isolate request process. The panel will include: 1) Ten isolates w/rifampin mono-resistance, including eight to nine unique rpoB mutations. 2) Ten isolates with FQ resistance including eight to nine unique gyrA mutations.
Would it be a good idea for us to apply for a support for the validation of FQs MICs on Sensititre under option 2
A:We are not being prescriptive with which testing method is used. You are free to propose evaluation of the methods that make the most sense for your laboratory. Applicants who already perform FQ testing are free to apply for Option 2 but should expect to score lower on Scorecard Question 3 than laboratories without FQ testing capability, as defined on page 16 of the RFP document.
What would be your expectations for the deliverables at the end of RFP period? Would it be acceptable if we would have evaluated FQ MIC testing with Sensititre plates, but let’s say, haven’t yet completed the formal validation by June 2024?
A:The expectation is that applicants will use the funds as described in question 7 (budget) and complete the work that is proposed in the RFP response (particularly with respect to question 4 (option 1) and / or question 5 (option 2)). Proposed timelines are required as part of the RFP response and the expectation is that the proposed timelines will be realistic with respect to the applicant’s capabilities. While a validation plan is also required as part of the RFP response, a completed method validation is not required as a final deliverable.
The final contract deliverable will be a progress report that should include a list of originally proposed activities, a description of the activities completed to date, definition of the next steps and an outcome statement. Ultimately the goal is to enable laboratories to update their practices, however we understand that evaluations are not always successful and that timelines may not perfectly align with the project period.
Are indirect costs allowable in the budget?
A:Indirect costs are allowed, however the final budget would still be subject to review and approval.
Was the informational call recorded and is it able to be shared?
A:Recording is available. The large file may take a minute to load