Aleksandra Barac1,2, Hannah Karimzadeh-Esfahani3, Mahya Pourostadi4, Mohammad Taghi Rahimi5, Ehsan Ahmadpour6,7, Jalil Rashedi8, Behroz Mahdavipoor9,10, Hossein Samadi Kafil11,12, Adel Spotin12, Kalkidan Hassen Abate13, Alexander G Mathioudakis14,15, Mohammad Asgharzadeh16. 1. Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia. 2. Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 3. Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK. 4. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 5. School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. 6. Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ehsanahmadpour@gmail.com. 7. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. ehsanahmadpour@gmail.com. 8. Tuberculosis and Lung Disease Research Center, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran. 9. Department of Laboratory Science, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran. 10. Department of Medical Parasitology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran. 11. Department of Microbiology, Tabriz University of Medical Sciences, Tabriz, Iran. 12. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 13. Institute of Health Sciences, Jimma University, Jimma, Ethiopia. 14. Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK. alexander.mathioudakis@manchester.ac.uk. 15. North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK. alexander.mathioudakis@manchester.ac.uk. 16. Faculty of Paramedicine, Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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.
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.
Authors: J D van Embden; M D Cave; J T Crawford; J W Dale; K D Eisenach; B Gicquel; P Hermans; C Martin; R McAdam; T M Shinnick Journal: J Clin Microbiol Date: 1993-02 Impact factor: 5.948
Authors: Annette T Nitta; Laura S Knowles; Jaimin Kim; Eleanor L Lehnkering; Lee A Borenstein; Paul T Davidson; Sydney M Harvey; Muriel L De Koning Journal: Am J Respir Crit Care Med Date: 2002-03-15 Impact factor: 21.405
Authors: F K C Ribeiro; E M Lemos; D J Hadad; S C Leão; C Viana-Niero; R Dietze; J L Johnson; K D Eisenach; M Palaci Journal: J Clin Microbiol Date: 2009-04-08 Impact factor: 5.948
Authors: Jasmine Ko Aqua; Jill Holdsworth; Eileen Burd; Jesse T Jacob; Susan M Ray; Marcos C Schechter Journal: J Investig Med High Impact Case Rep Date: 2021 Jan-Dec
Authors: Peter M Mbelele; Elingarami Sauli; Emmanuel A Mpolya; Sagal Y Mohamed; Kennedy K Addo; Sayoki G Mfinanga; Scott K Heysell; Stellah Mpagama Journal: Trop Med Int Health Date: 2021-06-24 Impact factor: 3.918