Grant Summary Report: Expansion of Nucleic Acid Amplification Testing for TB In Public Health Laboratories Angela M. Starks, Ph.D. Team Lead, Laboratory Capacity Team Laboratory Branch June 11, 2012 National Center for HIV/AIDS, Viral Hepatitis, STD & TB Prevention Division of TB Elimination
Strengthening the Laboratory System for Diagnosis of TB Overall Goal: Increase utilization and understanding of molecular diagnostics for detection of tuberculosis and drug resistance Rationale: Decreasing delays in laboratory diagnosis is a primary objective of DTBE and the Association of Public Health Laboratories (APHL). o Future of TB Laboratory Services (2002). Mechanism: Total of 3.0 million USD supplement awarded to APHL Capitalize on existing partnership with APHL o APHL has experience with providing technical assistance and funding to public health laboratories http://www.aphl.org/aphlprograms/infectious/documents/tb_task_force_future_2004.pdf
Reducing Delays in the Diagnosis of TB Objective 1: Support increased access to molecular diagnostics throughout the public health network. Rationale: 1. In 2009, public health laboratories performed nucleic acid amplification (NAA) testing for M. tuberculosis for 14% of TB suspects. 2. Updated Guidelines for the Use of Nucleic Acid Amplification Tests in the Diagnosis of Tuberculosis promoted the use of NAA testing as the standard of practice for TB suspects (MMWR, January 2009) 3. Goal aligns with expert panel recommendation from the Report of Expert Consultations on Rapid Molecular Testing to Detect Drug- Resistant Tuberculosis in the United States to utilize new funds for development/ strengthening of molecular drug-resistance testing programs.
Overview of NAA Test Grant Process Jurisdictions were invited to apply for a 6 month (Jan June 2011) sub-grant to expand NAA test services DTBE/ Laboratory Branch consulted with APHL to develop the request for and review of proposals in Nov/Dec 2010 2.6 million USD allocated for distribution via sub-grants for up to 64 public health laboratories to increase access to NAA testing Supported direct detection of M. tuberculosis complex or resistanceassociated mutations Funding utilized for reagents, instrumentation, contracts for referral service, courier systems, and training
Overview of NAA Testing Funding Proposals 56 of 64 eligible jurisdictions submitted either single or joint applications aimed at supporting in-house implementation or expanding existing programs Seven laboratories ceded funding or partnered to submit joint applications 8/64 eligible jurisdictions declined to submit an application Applications included implementation of NAA testing in three public health laboratories previously without access and one high-volume laboratory performing only limited testing on request. Seven laboratories with access through referral proposed testing inhouse.
Outcome of NAAT Sub-grant Final six-month project reports received July 2011 8 jurisdictions transitioned to a new method with others proposing new method continuing evaluation Majority examining new method were evaluating Cepheid GeneXpert MTB/RIF assay
Reported NAAT Methods Table 1. Number of Jurisdictions Reporting Current and Proposed NAAT Methods.* NAAT Method Current Method Continuing Evaluation Potential method after evaluation completed** GeneXpert MTB/RIF Assay 7 18 26 GeneProbe MTD 36 4 9 LDT real time-pcr 8 13 17 Total 51 35 52*** *As described in final report **Timeline unknown ***2 labs are conducting validation for two methods
Expansion of Capacity to Perform NAA Testing On average, compared to the same time period in 2010, jurisdictions reported an 85% increase in number of specimens tested by NAA Increased communication with submitters and targeted awareness campaigns to providers (e.g., infection control nurses and clinicians) Change in algorithm including additional testing of smear negative specimens On average, out of total number of specimens tested/referred for NAAT, 21% were also tested/referred for molecular detection of drug resistance Combination of increased interest in molecular results and validation of new methods
Reported Barriers to Completion of Plans During Project Period Barriers # Jurisdictions Limited samples for validation 12 Payment, contract, or approval mechanisms 11 Limited or loss of staff 9 Limited budget or funds 9
Reported Agreement Between Methods Of 659 patients with NAAT (+) specimens, 500 were AFB Smear (+) and 84 AFB Smear (-) 12 jurisdictions reported sensitivities and specificities comparing previous vs. new method 6 reported 100% sensitivity and 100% specificity for TB detection during validation Sensitivity was better for AFB Smear (+) than AFB Smear (-) specimens Lowest sensitivity and specificity reported for AFB Smear (+) was 98.2% and 100% respectively Lowest sensitivity and specificity reported for AFB Smear (-) was 72.5% and 62.5% respectively
Pulse Checks to Examine Sustainability Pulse checks will be conducted by APHL in 2012 to followup with awardees on continued and sustained progress Turnaround time Expansion of services to new patient populations Integration of new method into testing algorithm Sustainability of new methods (i.e., continued funding for reagents, maintenance, and supplies)