1. Achieving UniversAl g enotyping And the vAlUe of MolecUlAr dst
Erick Cortes, MPH1 Karen Galanowsky, RN, MPH 2 Natalia Kurepina, PhD 3 Barry Kreiswirth, PhD 4 Reynard McDonald MD 5
1
NJ Department of Health & Senior Services, 2NJ Department of Health & Senior Services, 3Public Health Research Institute, 4Public Health Research Institute, 5Global Tuberculosis Institute-Lattimore Chest Clinic
AbstrAct bAckground results CDC std.
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GD461, NJDOH In November 2009, a highly infectious asian male with pulmonary
Background: In January 2007, the New Jersey Department • When NJ’s universal genotyping project began in January • The efforts elaborated in the methods section above resulted TB walked into a NJ public health TB clinic. His CXR showed a RUL
of Health & Senior Services TB Program partnered with the 2007, there was no regulatory requirement for submission of in a systematic and efficient mechanism for requesting and cavity. He presented with a cough, fever, chills, night sweats and
Public Health Research Institute (PHRI) for IS6110 RFLP MTB isolates to the state laboratory. submission of isolates for genotyping. weight loss. He was started on RIPE. The contact investigation
analysis for positive MTB cultures as part of its universal found he lived with his wife and 8 month old child. The child’s
genotyping project. In July 2009, PHRI made molecular • No NJ hospitals and/or private providers used the state • These efforts resulted in a significant improvement in medical evaluation revealed a RLL infiltrate on CXR. The child was
DST available to public health TB clinics in NJ. also started on RIPE.
laboratory’s mycobacteriology services. the percentage of culture confirmed TB cases for whom
An investigation by the GC found that the source case’s initial
Methods: In early 2009, the TB Program’s Genotyping
genotyping results were available to 99.3% in CY2009.
• NJ’s healthcare providers used hospital and/or commercial specimen was shipped from a PA community hospital to a
Coordinator (GC) met individually with all hospital and laboratories both inside and out of state for these diagnostic tests. commercial reference laboratory in Chantilly, VA. The laboratory had
commercial laboratories operating in NJ to make them aware directed all results to the submitting physician. Since it was now
of a new regulation requiring the submission of all initial • The initial approach to secure isolates yielded a 70% known that the source case was a NJ resident, the GC requested
MTB isolates for genotyping. MOUs were signed with each that the laboratory submit a MTB isolate to PHRI under the TB
genotyping level in CY2007, decreasing to 65% in CY2008 Program’s existing MOU for genotyping.
of four out of state laboratories committing to submission
of requested isolates for residents of NJ. Molecular DST is An emergency TB slant was grown and submitted to PHRI for RFLP
requested by TB clinic staff through submission of a requisi- analysis and molecular DST. Only 9 days elapsed from the GC’s
tion to the GC. The GC confirms the sub-culture has either knowledge that a culture existed and its arrival at PHRI. Molecular
been requested and/or received by PHRI for genotyping, DST results identifying MDR-TB were available 5 days later and
and the molecular DST is done. Results are reported to the Methods conclusions RFLP was reported 7 days later. Conventional DST results were
not reported until 4 weeks later. The availability of molecular DST
TB clinic by the GC when known. allowed initiation of effective treatment for father and child long
• In April 2009, a regulation was adopted in NJ requiring • Sufficient regulatory requirements and effective working
before conventional DST results were even known.
Results: A conscientiously designed and executed strategy the submission of initial isolates to the state laboratory for relationships with laboratorians both inside and out of a state
for identifying and securing initial MTB isolates, including Molecular drug susceptibility testing based on the DNA sequencing
universal genotyping. are essential to the efficient submission of MTB isolates to
of target genes showed evidence of mutations in genes rpoB
the education of laboratorians both inside and outside NJ in achieve universal genotyping. (S531L), katG (S315T), and gyrA (D94G ). These mutations signify
the value of genotyping resulted in a 99.3% submission rate • The Genotype Coordinator (GC) met individually with all resistance to rifampin, isoniazid, and quinolones, respectively.
in CY2009. Access to molecular DST resulted in the more hospital and commercial laboratories operating within the • The local availability of RFLP provides actionable information Results were generated 5 days after slant submission to PHRI. Direct
timely initiation of effective treatment for an 8 month old state to make them aware of the new requirement, the value earlier than the regional genotyping laboratory. DST results confirmed the molecular resistance pattern four weeks
contact to a sputum smear and culture positive MDR-TB later. IS6110 RFLP designation was determined as GD461.
of genotyping to understanding the epidemiology of TB and
case in CY2009. • The local availability of RFLP improves turn-around times for Full band pattern results yielded:
to explain the notification and submission process for desired
isolates. spoligotyping and MIRU results from the regional genotyping Spoligotype Miru Miru 2 PCR Type
Conclusions: A systematic approach for identification,
requesting and submission of initial MTB isolates for ge- laboratory due to the submission of DNA, not MTB isolates 703777600001771 223625173533 424244223348 PCR13098
notyping and the nurturing of working relationships with • A MOU was signed with each of the four out-of-state from which DNA must be extracted.
multiple laboratory partners is essential to the efficient commercial laboratories providing mycobacterial services to Spoligotype Band Pattern
achievement of universal genotyping. The availability of NJ, securing a commitment to submit isolates upon request. nnnoooonnnnnnnnnnnnnooooooooooooooonnnnnnnn
molecular DST has substantial advantages over conventional
DST in the clinical management of patients with suspected NY_S00487 (703777600001771),
drug resistant disease and their contacts. belongs to M. tuberculosis CAS strain family