Volume 75, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Fever of unknown origin (FUO) poses a diagnostic challenge to the clinicians, with a differential diagnosis as varied as neoplastic and infectious diseases. In developing countries, the infectious causes are responsible for more cases of FUO, with tuberculosis as one of the main causes of classic FUO. Disseminated tuberculosis with negative pulmonary findings is a diagnostic problem. This study examines the diagnostic utility of the polymerase chain reaction (PCR) in samples of bone marrow aspirate in 85 patients presenting with diverse clinical symptoms. Using primers specific for , tubercular etiology was detected in 33% of patients clinically suspected of tuberculosis while culture on Lowenstein-Jensen medium grew in only one patient (2.5%). None of these patients had been diagnosed by microscopy. Clinical improvement with ATT was observed in 85% of the patients with positive PCR. PCR demonstrated much higher sensitivity and specificity, thereby facilitating early therapeutic decisions for suspected extrapulmonary tuberculosis.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Akcan Y, Tuncer S, Hayran M, Sungur A, Unal S, 1997. PCR on disseminated tuberculosis in bone marrow and liver biopsy specimens: correlation to histopathological and clinical diagnosis. Scand J Infect Dis 29 : 271–274. [Google Scholar]
  2. Kolk AH, Kox LF, van Leeuwen J, Kuijper S, Jansen HM, 1998. Clinical utility of the polymerase chain reaction in the diagnosis of extrapulmonary tuberculosis. Eur Respir J 11 : 1222–1226. [Google Scholar]
  3. Dar L, Sharma SK, Bhanu NV, Broor S, Chakraborty M, Pande JN, Seth P, 1998. Diagnosis of pulmonary tuberculosis by polymerase chain reaction for MPT64 gene: an evaluation in a blind study. Indian J Chest Dis Allied Sci 40 : 5–16. [Google Scholar]
  4. Kolk AH, Schuitema AR, Kuijper S, van Leeuwen J, Hermans PW, van Embden JD, Hartskeerl RA, 1992. Detection of Mycobacterium tuberculosis in clinical samples by using polymerase, chain reaction and a nonradioactive detection system. J Clin Microbiol 30 : 2567–2575. [Google Scholar]
  5. Verettas D, Kazakos C, Tilkeridis C, Dermon A, Petrou H, Galanis V, 2003. Polymerase chain reaction for the detection of Mycobacterium tuberculosis in synovial fluid, tissue samples, bone marrow aspirate and peripheral blood. Acta Orthop Belg 69 : 396–399. [Google Scholar]
  6. Maartens G, Willcox PA, Benatar SR, 1990. Miliary tuberculosis: rapid diagnosis, hematological abnormalities and outcome in 109 treated adults. Am J Med 89 : 291–296. [Google Scholar]
  7. Fonseca R, Tefferi A, 1997. Practical aspects in the diagnosis and management of aplastic anemia. Am J Med Sci 313 : 159–169. [Google Scholar]
  8. Roy A, Weisdorf D, 1997. Mycobacterial infections following bone marrow transplantation: a 20 year retrospective review. Bone Marrow Transplant 19 : 467–470. [Google Scholar]
  9. Kilby JM, Marques MB, Jaye DL, Tabereaux PB, Reddy VB, Waites KB, 1998. The yield of bone marrow biopsy and culture compared with blood culture in the evaluation of HIV-infected patients for mycobacterial and fungal infections. Am J Med 104 : 123–128. [Google Scholar]
  10. Seth P, Ahuja GK, Bhanu NV, Behari M, Bhowmik S, Broor S, Dar L, Chakraborty M, 1996. Evaluation of polymerase chain reaction for rapid diagnosis of clinically suspected tuberculous meningitis. Tubercle Lung Dis 77 : 353–357. [Google Scholar]
  11. Ritis K, Tzoanopoulos D, Speletas M, Papadopoulos E, Arvanitidis K, Kartali S, Sideras P, 2000. 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. J Intern Med 248 : 415–424. [Google Scholar]
  12. Escobedo-Jaimes L, Cicero-Sabido R, Criales-Cortez JL, Ramirez E, Romero M, Rivero V, Islas F, Olivera H, Gonzalez S, Escobar-Gutierrez A, 2003. Evaluation of the polymerase chain reaction in the diagnosis of miliary tuberculosis in bone marrow smear. Int J Tuberc Lung Dis 7 : 580–586. [Google Scholar]
  13. Kent PT, Kubica GP, 1985. Public Health Mycobacteriology: A Guide for the Level III Laboratory. Washington, DC: U.S. Department of Health and Human Services.
  14. George B, Mathews V, Srivastava V, Srivastava A, Chandy M, 2001. Tuberculosis among allogeneic bone marrow transplant recipients in India. Bone Marrow Transplant 27 : 973–975. [Google Scholar]
  15. Long R, O’Connor R, Palayew M, Hershfield E, Manfreda J, 1997. Disseminated tuberculosis with and without a miliary pattern on chest radiograph. Int J Tuberc Lung Dis 1 : 52–58. [Google Scholar]
  16. Albrecht H, Stellbrink HJ, Eggers C, Rusch-Gerdes S, Greten H, 1995. A case of disseminated Mycobacterium bovis infection in an AIDS patient. Eur J Clin Microbiol Infect Dis 14 : 226–229. [Google Scholar]
  17. Negi SS, Khan SFB, Gupta S, Pasha ST, Khare S, Lal S, 2005. Comparison of the conventional diagnostic modalities, bactec culture and polymerase chain reaction test for diagnosis of tuberculosis. Indian J Med Microbiol 23 : 29–33. [Google Scholar]
  18. Klatskin G, 1977. Hepatic granuloma: problems in interpretation. Mt Sinai J Med 44 : 798–812. [Google Scholar]
  19. Cutler RR, Baithun SI, Doran HM, Wilson P, 1994. Association between the histological diagnosis of tuberculosis and microbiological findings. Tubercle Lung Dis 75 : 75–79. [Google Scholar]
  20. Pierre C, Olivier C, Lecossier D, Boussougant Y, Yeni P, Hance AJ, 1993. Diagnosis of primary tuberculosis in children by amplification and detection of mycobacterial DNA. Am Rev Respir Dis 147 : 420–424. [Google Scholar]
  21. Baum SE, Dooley DP, Wright J, Kost ER, Storey DF, 2001. Diagnosis of culture-negative female genital tract tuberculosis with peritoneal involvement by polymerase chain reaction. J Reprod Med 46 : 929–932. [Google Scholar]
  22. Noordhoek GT, van Embden JD, Kolk AH, 1996. Reliability of nucleic acid amplification for detection of Mycobacterium tuberculosis: an international collaborative quality control study among 30 laboratories. J Clin Microbiol 32 : 2522–2525. [Google Scholar]
  23. Lombard EH, Victor T, Jordaan A, van Helden PD, 1995. The detection of Mycobacterium tuberculosis in bone marrow aspirate using the polymerase chain reaction. Tubercle Lung Dis 76 : 471. [Google Scholar]
  24. Geisler JP, Crook DE, Geisler HE, Cudahay TJ, Fraiz J, Bunce CP, Moore DK, Kay K, 2000. The great imitator: miliary peritoneal tuberculosis mimicking stage III ovarian carcinoma. Eur J Gynaecol Oncol 21 : 115–116. [Google Scholar]
  25. Chan KS, Looi LM, Chan SP, 1993. Disseminated histoplasmosis mimicking miliary tuberculosis: a case report. Malays J Pathol 15 : 155–158. [Google Scholar]
  26. Kim OH, Yang HR, Bahk YW, 1992. Pulmonary nocardiosis manifested as miliary nodules in a neonate: a case report. Pediatr Radiol 22 : 229–230. [Google Scholar]
  27. Mayo YWJ, Collazos J, Martinez E, 1997. Fever of unknown origin in the HIV-infected patient: new scenario for an old problem. Scand J Infect Dis 29 : 327–336. [Google Scholar]
  28. Ritis K, Giaglis S, Rafail S, Alepopoulou E, Tsironidou V, Tzoanopoulos D, Speletas M, Ktenidou-Kartali S, Sideras P, Kartalis G, 2005. Diagnostic usefulness of bone marrow aspiration material for the amplification of IS6110 insertion element in extrapulmonary tuberculosis: comparison of two PCR techniques. Int J Tuberc Lung Dis 9 : 455–460. [Google Scholar]
  29. Martino R, Martinez C, Brunet S, Sureda A, Lopez R, Domingo-Albos A, 1996. Tuberculosis in bone marrow transplant recipients: report of two cases and review of literature. Bone Marrow Transplant 18 : 809–812. [Google Scholar]
  30. Clarridge JE III, Shawar RM, Shinnick TM, Plikaytis BB, 1993. Large-scale use of polymerase chain reaction for detection of Mycobacterium tuberculosis in a routine mycobacteriology laboratory. J Clin Microbiol 31 : 2049–2056. [Google Scholar]
  31. Kirschner P, Rosenau J, Springer B, Teschner K, Feldmann K, Bottger EC, 1996. Diagnosis of mycobacterial infections by nucleic acid amplification: 18-month perspective study. J Clin Microbiol 34 : 304–312. [Google Scholar]
  32. Nolte FS, Metchock B, McGowan JE Jr, Edwards A, Okwumabua O, Thurmond C, Mitchell PS, Plikaytis B, Shinnick T, 1993. Direct detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction and DNA hybridisation. J Clin Microbiol 31 : 1777–1782. [Google Scholar]
  33. Hermans PWM, Schuitema AR, van Soolingen D, 1990. Specific detection of Mycobacterium tuberculosis complex strains by polymerase chain reaction. J Clin Microbiol 28 : 1204–1213. [Google Scholar]
  34. Buck GE, O’Hara LC, Summersgill JT, 1992. Rapid, simple method for treating clinical specimens containing Mycobacterium tuberculosis to remove DNA for polymerase chain reaction. J Clin Microbiol 30 : 1331–1334. [Google Scholar]
  35. Hellyer TJ, Desjardin LE, Assaf MK, Bates JH, Cave MD, Eisenach KD, 1996. Specificity of IS6110–based amplification assay for Mycobacterium tuberculosis complex. J Clin Microbiol 34 : 2843–2846. [Google Scholar]
  36. Choi YJ, Hu Y, Mahmood A, 1996. Clinical significance of a polymerase chain reaction assay for the detection of Mycobacterium tuberculosis. Am J Clin Pathol 105 : 200–204. [Google Scholar]

Data & Media loading...

  • Received : 25 Apr 2006
  • Accepted : 19 Jul 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error