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Quality assurance for molecular epidemiology of tuberculosis methods in the mycobacterium reference laboratory

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Abstract

In the National Mycobacterium Reference Laboratory of the Israeli National Public Health Laboratory (hereafter referred to as “the laboratory”), three methods are employed for the molecular epidemiology of Mycobacterium tuberculosis: IS6110 restriction fragment length polymorphism typing (RFLP typing), 43 spacer oligonucleotide typing (spoligotyping), and 24 loci Mycobacterial Interspersed Repeating Unit—Variable Number of Tandem Repeats typing (MIRU-VNTR typing). In this article, we describe the main practical aspects concerning quality assurance of these methods that are based on standardized, internationally agreed upon conditions, including consensus reference strains and markers. All three methods were validated by classical epidemiology (confirmed transmission) and clinical information. The laboratory has introduced a new 5 colors, 4 primer sets multiplex modification of the optimal 24-miru typing system that includes an easily produced in-house internal standard for the high-throughput capillary electrophoresis system. Quantitative measurement of the internal standards yielded statistics for measurement uncertainty that include the frequency distribution, mean, standard deviation, 95% confidence interval and coefficient of variation. Use of the new internal standard developed in our laboratory allowed us to introduce the first quantitative evaluation of the system performance of the AB3130xl capillary electrophoresis genetic analyzer for MIRU-VNTR typing. The results are discussed in terms of expected accuracy and precision of MIRU-VNTR results, and possible implications for forensic microsatellite typing which may be much more sensitive to the observed intra- and inter-plate variation.

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Acknowledgments

This work was performed under the auspices of the Israeli National Program for the Prevention and Control of Tuberculosis run by the Ministry of Health. We thank Daniel Chemtob, Head, and Zohar Mor, acting Head, of the Department of Tuberculosis and AIDS for their support. We also thank Noa Cedar for help with epidemiology, and all the Israeli National Mycobacterium Reference Laboratory staff and the health care staff of the Department of Tuberculosis and AIDS. The Israeli National Program for the Prevention and Control of Tuberculosis is supported by the efforts of health care professionals in hospitals and tuberculosis health care clinics, and we acknowledge their contribution to making possible the timely diagnosis and collection of new tuberculosis isolates. BCG P2 (one of our reference materials) was kindly provided by Hillel Bercovier, the Hebrew University of Jerusalem. MT14323 (another reference material) was kindly provided by the RIVM, the Netherlands, Dick van Soolingen and Kristen Kremer.

Conflict of interest

The authors assert that there is no conflict of interest associated with any author concerning the publication of this article.

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Authors and Affiliations

  1. National Mycobacterium Reference Laboratory, National Public Health Laboratory, Ministry of Health, Tel Aviv, Israel

    Paul J. Freidlin, Drora Goldblatt & Hasia Kaidar-Shwartz

  2. National Public Health Laboratory, Ministry of Health, Tel Aviv, Israel

    Zeev Dveyrin & Efrat Rorman

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  1. Paul J. Freidlin
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  2. Drora Goldblatt
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  3. Hasia Kaidar-Shwartz
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Correspondence to Paul J. Freidlin.

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Freidlin, P.J., Goldblatt, D., Kaidar-Shwartz, H. et al. Quality assurance for molecular epidemiology of tuberculosis methods in the mycobacterium reference laboratory. Accred Qual Assur 16, 623–635 (2011). https://doi.org/10.1007/s00769-011-0819-5

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