Misdiagnoses of Tuberculosis Resulting From Laboratory Cross-Contamination of Mycobacterium Tuberculosis Cultures—New Jersey, 1998

Morbidity and Mortality Weekly Report, May 19, 2000

A diagnosis of tuberculosis (TB) is rarely disputed if Mycobacterium tuberculosis is isolated from a clinical specimen; however, specimen contamination may occur (1-3). Identification of TB strain patterns through molecular typing or DNA fingerprinting is a recent advancement in TB laboratory techniques (3-7). COG'S National Tuberculosis Genotyping and Surveillance Network (NTGSN) performs DNA fingerprinting on TB isolates to determine the frequency of clustering among M. tuberculosis strains in project surveillance sites. In November 1998, NTGSN detected 11 isolates from previously reported TB cases among persons in New Jersey whose DNA fingerprints matched the avirulent laboratory M. tuberculosis control strain H37Ra. H37Ra does not cause active TB in humans, but it has been reported as a source of cross-contamination (8). In collaboration with the New Jersey Department of Health and Senior Services, COG investigated H37Ra as a possible cause of TB disease and/or TB misdiagnoses caused by laboratory cross- contamination in the 11 case-patients. This report describes findings from two of the 11 cases and summarizes the results of this investigation, which indicate that TB was misdiagnosed and demonstrate the value of DNA fingerprinting to identify occurrences of cross-contamination of patient specimens.

Case Findings

Case 1. In October 1998, a 44-year-old woman with multiple sclerosis and no known exposure to a person with active TB had TB diagnosed on the basis of a positive culture result. Cerebrospinal fluid revealed no signs of infection, butthe culture grew M. tuberculosis at 7 weeks. Her chest radiograph was normal, and a tuberculin skin test (TST) was not documented. Anti-TB therapy was not initiated because no development or progression of symptoms consistent with TB occurred. The cerebrospinal fluid was retested in the same laboratory (7 weeks after the original specimen was obtained) and revealed a stain with 1 acid-fast bacilli (AEB). The patient was started on anti-TB medications. The culture for the second specimen was negative for TB. This patient had received 4 months of anti-TB treatment at the time of the investigation.

Case 2. A 58-year-old woman with a history of reactive airway disease and angioedema was taken to a local emergency department with shortness of breath and cough. Her chest radiograph was normal, and a TST was not documented. A sputum specimen obtained at that time was AFB smear-negative, but M. tuberculosis culture was positive at 6 weeks. Although the patient had recovered after treatment for acute asthma, she was started on anti-TB treatment. Treatment was discontinued after 2 week when health-care providers determined her illness was not TB.

Summary Findings

A list of the 11 case-patients with an isolate with a fingerprint matching H37Ra was compiled, and information on the origin of each case-specimen was obtained. Investigators reviewed hospital, clinic, and health department records for each case-patient to establish the clinical events leading to TB diagnosis. Investigators visited the laboratories where the 11 specimens were processed to interview laboratory personnel about specimen processing techniques and to review laboratory logs for mycobacterial specimen testing.

The 11 case-patients had TB diagnosed and reported during 1996-1998. Mean age of patients was 60 years (range: 36-81 years); eight were women, and three were human immunodeficiency virus (HIV)-positive. Eight cases were classified as pulmonary and three as extrapulmonary. Seven patients had abnormal chest radiograph findings, and two had documented positive TSTs. All case-patients received partial or full-course therapy for TB; treatment durations ranged from 2 weeks to 6 months. Seven patients had contact investigations performed; four of the 32 contacts identified were tested and treated for latent TB infection. Each case met at least one criterion for suspected laboratory cross-contamination with M. tuberculosis [*]. In addition, each of the eight pulmonary patients had clinical courses suggestive of an illness other than TB (i.e., bacteria pneumonia [four], reactive airways disease [two], interstitial lung disease [one], and congestive heart failure [one]).

The laboratory investigation revealed that the 11 specimens were processed during February 1996-October 1998 at four laboratories in New Jersey (three hospital laboratories and one commercial laboratory). Each of the laboratories either used the strain H37Ra or participated in laboratory proficiency testing using H37Ra; however, laboratory logs did not include the specific times when H37Ra was handled on the same day as any of the 11 specimens. In addition, personnel at the laboratories could not recall instances when the control strain may have been mishandled. The average number of specimens collected for AFB culture per patient was four (range: two to 12). All culturepositive patient specimens were smear-negative. Mean number of days to M. tuberculosis growth for patient specimens was 38 (range: 17-54 days).