Correspondence

PCR and the Misdiagnosis of Active Tuberculosis

N Engl J Med 1995; 332:128-129January 12, 1995

Article

To the Editor:

Noordhoek et al. (Dec. 30, 1993, issue)1 have raised serious questions1,2 about the reliability of the polymerase chain reaction (PCR) for the direct detection of Mycobacterium tuberculosis in clinical specimens. Nevertheless, commercial clinical laboratories continue to promote many PCR assays, even for use by correctional facilities.

After a routine medical evaluation at the time of her entry into a state correctional facility, an asymptomatic 28-year-old woman had a 20-mm reaction to a purified-protein-derivative tuberculin skin test (Mantoux method). Her chest roentgenogram was normal. Three sputum specimens were collected on separate days for mycobacterial laboratory studies. Although no acid-fast bacilli were seen on the smears of any specimens with auramine–rhodamine fluorescence staining, two specimens were positive for M. tuberculosis by a PCR direct-detection test at a contract laboratory. On the basis of the results of the PCR tests alone, isolation precautions against acid-fast bacilli were implemented, the patient received a four-drug antituberculosis regimen, and an investigation of contacts was begun.

In the subsequent evaluation, three more sputum smears tested negative for acid-fast bacilli, a second chest roentgenogram was interpreted as “old granulomatous disease — no active disease,” and a serologic test for human immunodeficiency virus was negative. When the first three mycobacterial cultures showed no growth after four weeks, the isolation precautions were discontinued and the treatment regimen was reduced to isoniazid alone as preventive therapy. Ultimately, all six mycobacterial cultures had no growth.

Although there was no other evidence of active tuberculosis, the results of two direct PCR tests of sputum specimens for M. tuberculosis were positive and a diagnosis of active tuberculosis was made. The woman received unnecessary medications, and the prolonged isolation precautions and contact investigations were also unnecessary, especially since the acid-fast–bacilli smears were negative.

In September 1993, the Public Health Service noted that commercial laboratories are promoting PCR assays for the rapid detection of M. tuberculosis in clinical specimens. The rates of false positive and false negative results and the predictive value of these tests remain unclear. The tests are still under investigation by the Food and Drug Administration and should not be part of routine clinical use.3

Abe Macher, M.D.
Eric Goosby, M.D.
Public Health Service, Rockville, MD 20857

3 References

1. 1

   Noordhoek GT, van Embden JDA, Kolk AHJ. Questionable reliability of the polymerase chain reaction in the detection of Mycobacterium tuberculosis. N Engl J Med 1993;329:2036-2036
   Full Text | Web of Science | Medline

2. 2

   Noordhoek GT, Kolk AH, Bjune G, et al. Sensitivity and specificity of PCR for detection of Mycobacterium tuberculosis: a blind comparison study among seven laboratories. J Clin Microbiol 1994;32:277-284
   Web of Science | Medline

3. 3

   Diagnosis of tuberculosis by nucleic acid amplification methods applied to clinical specimensMMWR Morb Mortal Wkly Rep 1993;42:686-686
   Medline

Citing Articles (2)

Citing Articles

1. 1

   Paul Kelly, Filomena Pereira-Maxwell, Simon Carnaby, Ian White. (2005) Confidence in polymerase chain reaction diagnosis can be improved by Bayesian estimation of post-test disease probability. Journal of Clinical Epidemiology 58:3, 252-260
   CrossRef

2. 2

   Sho Yamasaki, Osamu Sugita, Masanobu Tanimura, Masaaki Morioka. (1996) Tuberculoma Arising in the Inguinal Portion of the Spermatic Cord: A Case Report. International Journal of Urology 3:6, 514-517
   CrossRef