False-Positive Investigation Toolkit: Monitoring for False-Positive Results Outside the Laboratory

Key points

Retrospective identification of false-positive MTBC results is accomplished through active and passive surveillance by both TB Programs and healthcare providers. This monitoring is critical in addition to laboratory monitoring. Communication between TB Programs, healthcare providers, and laboratories must remain open and is essential when results are questionable.

TB Program

Through monitoring or review of case results, the TB Program should alert the testing laboratory and healthcare provider of any patient suspected of having a false-positive result and an investigation should be initiated. Based on evidence from the investigation, genotyping can be requested (if not already reported) from the National Tuberculosis Molecular Surveillance Center to aid in the determination of a false-positive result. If the investigation leads to the conclusion that a false-positive result is likely, the TB Program should:

  • Communicate with the laboratory to make an assessment and determine the likelihood of false-positives,
  • Alert the healthcare providers so that the patient can be correctly diagnosed and treated (therapy discontinued or modified),
  • Alert the healthcare facility or laboratory involved so that the cause of the false-positive result can be investigated and corrected1, and
  • Alert surveillance staff to ensure accuracy of documented laboratory results and case counts.

Monitoring by TB Programs consists of two main areas:

  1. Review of patients with positive cultures
  2. Molecular epidemiology

Medical records should be reviewed and healthcare providers should be communicated with to identify patients who, despite a positive test for MTBC, do not fit the typical clinical presentation:

  • Patients diagnosed with pulmonary TB who exhibit normal chest radiographs
  • Patients diagnosed with a different condition before TB culture results are reported
  • Patients with a negative interferon gamma release assay (IGRA) ortuberculin skin test (TST) result
  • Patients not started on treatment for TB
  • Patients started on TB treatment only after culture results were reported
  • Patients with multiple specimens but only one culture positive for MTBC
  • Patients with follow-up specimens collected to monitor treatment response (i.e., culture conversion) that only grew NTMs

Identical genotyping results for those specimens tested in the same batch derived from multiple patients should be verified with clinical presentation or epidemiology.

  • Recognize patients with identical genotypes and confirm a relationship using epidemiologic links.
  • Identify genotypes within a jurisdiction that are uncommon.
  • Recognize laboratory PT or QC strain genotypes.

TB programs might investigate:

Route of the patients' specimens from collection to receipt in the laboratory to identify possible pre–analytic errors that could have resulted in contamination or mislabeling.

Sputum collection

  1. Where (TB Clinic, hospital, clinical laboratory, home)
  2. When (collected at same time as other patient specimens
  3. How (routine collection, induced sputum, bronchoscope use)
  4. What (collection container issues)
  5. Who (patient by themselves, or overseen by a provider)

Specimen labeling/requistion forms

Genotyping results as a part of TB control practices

  • Review epidemiology of patients within a genotype cluster to aid in determination of a false-positive result (e.g., rare strains in multiple patients over a short time span, matching genotypes among seemingly unrelated patients, and unexpected strains based on patient demographics)
  • Review discordant genotypes among specimens from the same patient
  • Compare genotypes to QC strains or laboratory PT strains that have been submitted for genotyping

Health Care Providers

A healthcare provider may suspect a false-positive laboratory result when a patient has a positive TB test result but no signs/symptoms of TB, clinical presentation that is inconsistent with TB, or radiographic findings that are inconsistent with TB. In addition, a healthcare provider may suspect cross-contamination if multiple specimens have been submitted for a patient and only one is culture-positive, while all have negative AFB smears34. Other patient indicators that may initiate a false-positive TB investigation include:

  • Patient has no risk factors for TB,
  • Negative IGRA or TST result,
  • Chest radiograph not improved after two or more months of anti-tuberculosis medications,
  • New positive culture in a patient who previously culture converted,
  • New positive culture with a different susceptibility pattern,
  • History of previous NTM infection, and/or
  • Follow-up cultures for monitoring treatment response (i.e., culture conversion) only grow NTMs.
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Content Source:
Division of Tuberculosis Elimination ; National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention; Centers for Disease Control and Prevention
  1. Centers for Disease Control and Prevention (CDC). Guide to the application of genotyping to tuberculosis prevention and control. 2012. https://www.cdc.gov/tb/programs/genotyping/chap6/6_apply_3_suspected.htm
  2. Tuberculosis Clinical Policies and Protocols Manual. 4th ed. Bureau of Tuberculosis Control. New York City Department of Health and Mental Hygiene. 2008. https://www1.nyc.gov/site/doh/providers/health-topics/tb-hosp-manual.page
  3. Poynten, M, Andresen DN, Gottlieb. Laboratory cross-contamination of Mycobacterium tuberculosis: an investigation and analysis of causes and consequences. Internal Med J 2002 Nov;32(11):512-9.
  4. MMWR. Misdiagnoses of Tuberculosis Resulting From Laboratory Cross-Contamination of Mycobacterium Tuberculosis Cultures — New Jersey, 1998 2000 May 19;49(19):413-6.