APTIMA COMBO 2 ASSAY

Description of Event or Problem

INITIAL AND FINAL REPORT. ON (B)(6) 2020, A CUSTOMER CALLED REGARDING AC2 RESULTS RUN ON THE PANTHER INSTRUMENT. THE CUSTOMER REPORTED TESTING A ENDOCERVICAL SWAB TWICE RESULTING BOTH TIMES IN CHLAMYDIA TRACHOMATIS (CT) EQUIVOCAL/NEISSERIA GONORRHOEAE (GC) NEGATIVE RESULTS. A SECOND URINE SAMPLE WAS PROVIDED FROM THE SAME PATIENT, AND ALSO PRODUCED AC2 CHLAMYDIA TRACHOMATIS (CT) EQUIVOCAL/NEISSERIA GONORRHOEAE (GC) NEGATIVE RESULTS. HOLOGIC REVIEWED THE PANTHER LOGS AND CONFIRMED THE RESULTS PROVIDED BY THE CUSTOMER. THE REVIEW OF THE LOGS DID NOT IDENTIFY ANY HARDWARE ISSUES OR REAGENT PREPARATION ISSUES IN THE WORKLISTS ASSOCIATED WITH THESE SAMPLES. HOLOGIC REQUESTED THE RETURN OF THESE SAMPLES FOR FURTHER ANALYSIS. HOLOGIC REPEATED THE AC2 TESTING OF THESE TWO SAMPLES AND REPLICATED THE CT EQUIVOCAL/GC NEGATIVE RESULT WITH EACH SAMPLE. ON (B)(6) 2020, HOLOGIC PERFORMED SEQUENCING OF THE SAMPLES AND IDENTIFIED THAT THE SAMPLES FROM THIS PATIENT CONTAINED A SINGLE BASE CHANGE COMPARED TO PUBLISHED C. TRACHOMATIS 23S RRNA SEQUENCES. TESTING AT HOLOGIC OF IN VITRO TRANSCRIPT RNA HAS DEMONSTRATED THAT THIS VARIANT AFFECTS CT DETECTION BY AC2. RISK ASSESSMENT WAS PERFORMED BY HOLOGIC AND DETERMINED THAT PROBABILITY OF HARM IS REMOTE. IN THIS CASE, THE PATIENT SAMPLES PRODUCED EQUIVOCAL RESULTS AND THE PATIENT RECEIVED TREATMENT FOR A CT INFECTION. IN ADDITION, THIS IS ONLY THE SECOND KNOWN CT VARIANT SAMPLE WITH A MUTATION IN THE RRNA REGION UTILIZED IN THE AC2 ASSAY IN UNITED STATES. IN JUNE 2019, HOLOGIC PREVIOUSLY IDENTIFIED A SEPARATE U.S. SAMPLE THAT ALSO CONTAINED THE G1526A CT VARIANT ((B)(4)). FOR PERSPECTIVE ON POTENTIAL PREVALENCE, HOLOGIC HAS SOLD OVER (B)(4) AC2 TESTS IN THE UNITED STATES SINCE OCTOBER 2018. SEVERAL RECENT PUBLICATIONS DEMONSTRATE COMPARABLE PERFORMANCE OF THE AC2 ASSAY WITH OTHER MANUFACTURERS' ASSAYS.1-7 REFERENCES: BRISTOW CC, ET AL. COMPARATIVE EVALUATION OF 2 NUCLEIC ACID AMPLIFICATION TESTS FOR THE DETECTION OF CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE AT EXTRAGENITAL SITES. SEX TRANSM DIS. 2017; 44(7): 398-400. DOI: 10.1097/OLQ.0000000000000627. COSENTINO LA, ET AL. USE OF NUCLEIC ACID AMPLIFICATION TESTING FOR DIAGNOSIS OF EXTRAGENITAL SEXUALLY TRANSMITTED INFECTIONS. J CLIN MICROBIOL. 2017; 55(9): 2801-2807. DOI: 10.1128/JCM.00616-17. DIZE L, ET AL. COMPARISON OF THE CEPHEID GENEXPERT CT/NG ASSAY TO THE HOLOGIC APTIMA COMBO2 ASSAY FOR THE DETECTION OF CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE IN SELF-COLLECTED RECTAL SWABS. DIAGN MICROBIOL INFECT DIS. 2018; 90(2): 83-84. DOI: 10.1016/J.DIAGMICROBIO.2017.10.013. GEIGER R, ET AL. VALIDATION OF THE GENEXPERT® CT/NG ASSAY FOR USE WITH MALE PHARYNGEAL AND RECTAL SWABS. AUSTIN J HIV AIDS RES. 2016; 3(1): PII: 1021. NYE MB, ET AL. DETECTION OF CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE WITH THE COBAS CT/NG V2.0 TEST: PERFORMANCE COMPARED WITH THE BD PROBETEC CT QX AND GC QX AMPLIFIED DNA AND APTIMA AC2 ASSAYS. SEX TRANSM INFECT. 2019; 95(2): 87-93. DOI: 10.1136/SEXTRANS-2018-053545. VAN DER POL B, ET AL. EVALUATION OF THE PERFORMANCE OF THE COBAS CT/NG TEST FOR USE ON THE COBAS 6800/8800 SYSTEMS FOR DETECTION OF CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE IN MALE AND FEMALE UROGENITAL SAMPLES. J CLIN MICROBIOL. 2019; 57(4): PII: E01996-18. DOI: 10.1128/JCM.01996-18. VENTER JME, ET AL. COMPARISON OF AN IN-HOUSE REAL-TIME DUPLEX PCR ASSAY WITH COMMERCIAL HOLOGIC® APTIMA ASSAYS FOR THE DETECTION OF NEISSERIA GONORRHOEAE AND CHLAMYDIA TRACHOMATIS IN URINE AND EXTRA-GENITAL SPECIMENS. BMC INFECT DIS. 2019; 19(1): 6. DOI: 10.1186/S12879-018-3629-0.