Economic evaluation of the use of PCR assay in diagnosing pulmonary TB in a low-incidence area. I. Rajalahti, E-L. Ruokonen, T. Kotomäki, H. Sintonen, M.M. Nieminen. #ERS Journals Ltd 2004. ABSTRACT: To determine whether polymerase chain reaction (PCR) testing in the initial diagnosis of pulmonary tuberculosis (TB) is cost-effective in a low-prevalence population, an economic evaluation was carried out between the smear and culture (NOPCR) and smear, culture and PCR (zPCR) strategies.A decision tree model based on retrospective laboratory data was developed to assess the strategies of testing patients with suspicion of TB. Direct healthcare costs prior to confirmation of TB or nontuberculous mycobacteria by PCR or culture were included. Effectiveness was measured by the probability of correct treatment and isolation decisions.In the baseline situation NOPCR costs J29.50 less than the zPCR strategy per patient tested. According to sensitivity analyses, reducing PCR test price, shortening test performance time or increasing the proportion of smear-positive patients in the tested population would contribute to cost savings with the zPCR strategy.Routine polymerase chain reaction testing of all specimens from suspected tuberculosis patients in a low-prevalence population was not cost-saving. When the polymerase chain reaction assay was applied only to smear-positive sputum specimens, the smear and culture strategy was clearly dominated by it, i.e. the polymerase chain reaction smear-positive sputum strategy was less costly and more effective in producing correct treatment decisions and isolations. To date the global tuberculosis (TB) epidemic has shown no notable decline. In low-prevalence countries, factors contributing to the spread of the disease, especially in hospital settings, are delays in diagnosis and initiation of treatment [1]. In addition to lack of suspicion of TB, diagnosis is prolonged by the time-consuming identification of the Mycobacterium tuberculosis complex in sputum specimens [2]. The acid-fast smear rapidly identifies patients with infectious TB, but is neither sensitive nor specific for M. tuberculosis bacteria. In countries like Finland (494 TB cases and 505 cases with nontuberculous mycobacteria in 2001) where nontuberculous mycobacteria are frequently detected, smear-positive nontuberculous cases may be isolated and treated with inappropriate drug combinations unnecessarily until culture results are available. Culture is sensitive in detecting mycobacteria for species identification and susceptibility testing, but requires a mean time of 2-3 weeks [3]. In smear-negative TB cases this may lead to unnecessary diagnostic procedures that increase healthcare costs and cause distress to the patients.Commercial nucleic acid amplification (NAA) assays are rapid, sensitive and specific tools for the detection of the M. tuberculosis complex in sputum specimens [4][5][6]. In addition to rapid differentiation between this complex and nontuberculous mycobacteria in smear-positive sputum specimens, NAA ...

Three hundred twenty-four sputum specimens from 151 patients with suspected active pulmonary tuberculosis were tested for the presence of the Mycobacterium tuberculosis complex with auramine fluorochrome stain and automated PCR assay (Roche Cobas Amplicor Mycobacterium Tuberculosis Test [MTB]). The results were compared with those of the conventional Löwenstein-Jensen tube culture and the BACTEC radiometer liquid culture. A total of 76 specimens from 32 patients were culture positive for M. tuberculosis. In addition, 37 specimens from 15 patients were smear and culture positive for other Mycobacterium species but negative by the present nucleic acid amplification method and thus were not included in the comparison. Compared with culture, the sensitivities, specificities, and positive and negative predictive values for acid-fast smear were 67, 98, 93, and 91% and those for the Cobas Amplicor MTB were 83, 99, 97, and 95%, respectively. When three consecutive sputum specimens per patient could be obtained, the sensitivity of the Cobas Amplicor MTB improved to 91%, whereas the sensitivity of the acid-fast smear remained unchanged.

To evaluate the clinical utility of the DNA and RNA amplification assays in monitoring the efficacy of tuberculosis treatment, 416 sputum specimens collected from 15 smear-positive tuberculosis patients during and after treatment were tested for the presence of Mycobacterium tuberculosis by microscopy, culture, polymerase chain reaction (Cobas Amplicor Mycobacterium Tuberculosis Test; Roche, Switzerland) and AMTDT 2 (Amplified Mycobacterium Tuberculosis Direct Test; Gen Probe, USA). All patients were cured, and no relapses were found. Results of both amplification assays re mained positive longer than results of either smear or culture. Four of 15 patients were positive by polymerase chain reaction and/or AMTDT 2 at the completion of treatment. Subsequent sputum specimens from these patients converted to negative within 2.5-12 months. The present data do not support the routine use of qualitative amplification assays for monitoring the treatment response of smear-positive tuberculosis patients.

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