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

Objectives. Extrapulmonary tuberculosis (TB) constitutes the main cause of classic fever of unknown origin (FUO) in many populations. The aim of this study was to improve the diagnostic field of the disease using a nested pol ymerase chain reaction (PCR) assay, specific for the IS6110 insertion eleme nt of Mycobacterium tuberculosis complex, in order to achieve a more timely diagnosis and treatment. Setting. Twenty-four, HIV-negative classic FUO patients who were admitted t o the Regional Hospital of Alexandroupolis between April 1997 and July 1999 . Subjects and design. The above patients were considered as putative extrapu lmonary TB after 3 weeks of in-patient investigation and underwent exhausti ve examination for diagnosis of the disease. For this purpose peripheral bl ood patients, as well as from damaged tissues, and analysed by both PCR and conventional methods. Anti-tuberculous treatment was initiated in 16 out o f 24 patients and the response to this regimen was considered as the final criterion for diagnosis of tuberculosis. Results. Extrapulmonary TB was established in 11 patients. The PCR-based me thodology, when applied to samples derived from bone marrow aspirations and suspected damaged tissues, was able to diagnose 10 of them, whereas the co nventional methods were able to detect only two. Conclusions. Our results confirm the diagnostic value of molecular detectio n of M. tuberculosis in cases of FUO, thus supporting the application of PC R in tissue samples suspected of bacillus infection. Furthermore, our studi es demonstrate that bone marrow aspiration specimens constitute an alternat ive, easy, safe and reliable source for such PCR analysis.