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Laboratory Cross-Contamination of Mycobacterium tuberculosis: A Systematic Review and Meta-analysis

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Abstract

Background

Microbiological cultures are the mainstay of the diagnosis of tuberculosis (TB). False-positive TB results lead to significant unnecessary therapeutic and economic burden and are frequently caused by laboratory cross-contamination. The aim of this meta-analysis was to quantify the prevalence of laboratory cross-contamination.

Methods

Through a systematic review of five electronic databases, we identified studies reporting rates of laboratory cross-contamination, confirmed by molecular techniques in TB cultures. We evaluated the quality of the identified studies using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and conducted a meta-analysis using standard methodology recommended by the Cochrane Collaboration.

Results

Based on 31 eligible studies evaluating 29,839 TB cultures, we found that 2% (95% confidence intervals [CI] 1–2%) of all positive TB cultures represent false-positive results secondary to laboratory cross-contamination. More importantly, we evaluated the rate of laboratory cross-contamination in cases where a single-positive TB culture was available in addition to at least one negative TB culture, and we found a rate of 15% (95% CI 6–33%). Moreover, 9.2% (91/990) of all patients with a preliminary diagnosis of TB had false-positive results and received unnecessary and potentially harmful treatments.

Conclusions

Our results highlight a remarkably high prevalence of false-positive TB results as a result of laboratory cross-contamination, especially in single-positive TB cultures, leading to the administration of unnecessary, harmful treatments. The need for the adoption of strict technical standards for mycobacterial cultures cannot be overstated.

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Abbreviations

HIV:

Human immunodeficiency virus

MDR-TB:

Multidrug-resistant tuberculosis

NIH:

National Institute of Health

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

TB:

Tuberculosis

WHO:

World Health Organization

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Acknowledgement

This study was supported by the Iranian National Sciences Foundation (Grant No: 843599) and Tabriz University of Medical Sciences (Grant No: 37876). AGM is supported by the National Institute for Health Research Manchester Biomedical Research Centre (NIHR Manchester BRC). Dr Aleksandra Barac’s scientific work and research is supported by the Project of Ministry of Education, Science and Technology of the Republic of Serbia (No. III45005).

Author information

Author notes

  1. Aleksandra Barac and Hannah Karimzadeh-Esfahani have contributed equally to this work.

Authors and Affiliations

  1. Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia

    Aleksandra Barac

  2. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Aleksandra Barac

  3. Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK

    Hannah Karimzadeh-Esfahani & Alexander G. Mathioudakis

  4. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahya Pourostadi

  5. School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Mohammad Taghi Rahimi

  6. Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ehsan Ahmadpour

  7. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Ehsan Ahmadpour

  8. Tuberculosis and Lung Disease Research Center, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Jalil Rashedi

  9. Department of Laboratory Science, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Behroz Mahdavipoor

  10. Department of Medical Parasitology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran

    Behroz Mahdavipoor

  11. Department of Microbiology, Tabriz University of Medical Sciences, Tabriz, Iran

    Hossein Samadi Kafil

  12. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Hossein Samadi Kafil & Adel Spotin

  13. Institute of Health Sciences, Jimma University, Jimma, Ethiopia

    Kalkidan Hassen Abate

  14. North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK

    Alexander G. Mathioudakis

  15. Faculty of Paramedicine, Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mohammad Asgharzadeh

Authors
  1. Aleksandra Barac
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  2. Hannah Karimzadeh-Esfahani
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Contributions

MP, HK, MTR, EA, AB, JR, BM, HSK, AGM, and MA carried out the systematic review and meta-analyses and drafted the manuscript. AGM provided methodological expertise. AS, KHA, MA, and EA participated in the design of the study and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Ehsan Ahmadpour or Alexander G. Mathioudakis.

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408_2019_241_MOESM1_ESM.docx

Causes of M. tuberculosis cross-contamination that were identified in the included studies. Supplementary material 1 (DOCX 38 kb)

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Barac, A., Karimzadeh-Esfahani, H., Pourostadi, M. et al. Laboratory Cross-Contamination of Mycobacterium tuberculosis: A Systematic Review and Meta-analysis. Lung 197, 651–661 (2019). https://doi.org/10.1007/s00408-019-00241-4

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  • DOI: https://doi.org/10.1007/s00408-019-00241-4

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