Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis

Abstract

aaMicroscopy with the auramine or Ziehl-Neelsen (ZN) stain is frequently negative in cases of extrapulmonary tuberculosis (TB). This means that treatment may be started and continued until the culture results confirm or refute the diagnosis at least 3 weeks later. The polymerase chain reaction (PCR), which permits direct identification of the Mycobacterium tuberculosis complex [1, 2] is more sensitive than microscopy, has a much lower detection limit and gives results within 24 h of receipt of the sample. The few studies which have evaluated PCR for the diagnosis of extrapulmonary TB have included a high percentage of human immunodeficiency virus (HIV)-seropositive patients. The sensitivity of PCR in these studies ranges 42-93% [3][4][5][6]. Previously, we and others showed that PCR can be used for the detection of pulmonary TB cases in routine laboratories [7][8][9]. Using our improved PCR technique [2], we evaluated the contribution of PCR to the diagnosis of TB in patients suspected of having extrapulmonary TB. Patients with suspected tuberculous meningitis were excluded from this analysis and are the subject of a separate publication [10]. Materials and methods PatientsTwo hundred and twenty six specimens were obtained from 156 patients residing in the Netherlands who were suspected of having TB on the basis of symptoms, signs and radiological findings as judged by the treating clinician at the time of presentation. None of the patients had a recent (ð5 yrs) diagnosis of mycobacterial disease. The specimens were taken before antituberculous treatment was started.Comparisons between conventional techniques (microscopy and culture) and PCR were made on samples from a single specimen. The specimens were obtained from various tertiary hospitals in the Netherlands and were sent by regular mail at ambient temperature to the Royal Tropical Institute. They arrived within 48 h and were processed on the same day and stored at 4°C. The specimens included pleural fluid (n=55), tissue biopsies (n=52), blood (n=56), pus from wound (n=32), bone marrow (n=6), ascites (n= 2), synovial fluid (n=5), pericardial fluid (n=3), urine (n= 13) and faeces (n=2). Treatment of specimensOn receipt at the local laboratory, the specimen was split and a portion was sent to us for testing with PCR. The remaining portion was handled as detailed below. Protocols for specimen processing were standardized [11].Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis. A.H.J. Kolk, L.F.F. Kox, J. van Leeuwen, S. Kuijper, H.M. Jansen. ©ERS Journals Ltd 1998. ABSTRACT: This study examines the diagnostic utility of the polymerase chain reaction (PCR) in 156 patients (five human immunodeficiency virus (HIV) seropositive) suspected of extrapulmonary tuberculosis.The results of PCR in 226 samples from 11 different sites were compared with the results of microscopy and culture.Positive culture results were predicted in 86% of samples by PCR but in only 31% by microscopy. Specificity of PCR was 92%. In cases with...

Amplification of IS6110 sequence for detection of Mycobacterium tuberculosis complex in HIV‐negative patients with fever of unknown origin (FUO) and evidence of extrapulmonary disease

“…However, the diagnostic yield of PCR in HIV-seronegative patients suffering from extrapulmonary TB was very low in peripheral blood, bone marrow, urine, and pleural or pericardial fluid [13,14,25,26]. Furthermore, earlier reports failed to demonstrate the validity of PCR amplification for diagnosis FUO in HIV-negative cases of extrapulmonary TB [13,25,26]. Although our study included a relatively small number of FUO patients, it nevertheless demonstrated the high sensitivity of the applied PCR protocol in bone marrow and/or in samples obtained from suspected tissues of Mycobacterium contamination.…”

Rapid Diagnosis of Tuberculous Pleural Effusion by IS6110 Sequence Based PCR

“…Earlier studies reported the positivity of the M. tuberculosis complex by PCR targeting the IS6110 element in specimen wise distribution of the M. tuberculosis complex in EPTB. Tiwari et al, [22] Maurya A K et al, [23] S. Nagesh et al, [26] Portillo -Gomez L, et al, [27] Kolk, AHJ et al, [28] Sekar B et al, [29] showed the detection of the M. tuberculosis complex in the pleural fluid by PCR results as summarized in Table 4. In our study we found 70% positivity in PCR targeting the IS6110 element in pleural fluid specimens.…”

Clinical usefulness of the nested polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis

“…35 In the present study, PCR exhibited greater sensitivity than microscopy and the culture, and could facilitate therapeutic decisions for patients with a clinical suspicion of ETB; as was found by other authors. [36][37][38] For diagnosis of GUTB, although a high index for clinical suspicion is necessary, 39 PCR can be useful for cases in which bacteriologic and clinical diagnoses of TB are not conclusive. 40 We found PCR to be a very rapid diagnostic method for GUTB.…”