Since Robert Koch described the cause of tuberculosis in 1882, the natural history of the disease after primary infection has been subject to debate. Only approximately 10% of infected individuals develop active disease, which may appear years to decades after infection. Late onset has been attributed to the endogenous reactivation of dormant bacteria. However, this has not been documented by molecular means for latencies of more than a few years. In Denmark, we have recently recultured 205 freeze-dried Mycobacterium tuberculosis strains obtained from 1961 through 1967. These "historical" strains are analyzed by DNA restriction fragment-length polymorphism testing, and their DNA patterns are compared with those of 4008 recently obtained clinical specimens. This has, surprisingly, yielded molecular evidence of M. tuberculosis reactivation after 33 years of latent infection. A father and son who developed tuberculosis in 1961 and in 1994, respectively, were the only patients infected with strains that share an identical DNA pattern.

A new immunodiagnostic test based on the Mycobacterium tuberculosis-specific antigens CFP-10/ESAT-6(QFT-RD1) has been launched as an aid in the diagnosis of latent tuberculosis (TB) infection (LTBI). The aim of this study was to evaluate this test for the diagnosis of active TB. Eighty-two patients with suspicion of TB and 39 healthy BCG-vaccinated persons were enrolled. Forty-eight had active TB, 25 did not, and 9 were excluded. Sensitivity and specificity of the test for active TB were evaluated in a prospective blinded manner in patients suspected of TB. The sensitivity of the QFT-RD1 was 85% (40/48; confidence interval [CI], 75 to 96), and it was higher than the sensitivity of microscopy, 42% (20/48; CI, 27 to 56; P ‫؍‬ 0.001), and culture, 59% (27/46; CI, 44 to 73; P ‫؍‬ 0.009). Of patients with extrapulmonary TB, 92% (12/13) were QFT-RD1 positive, whereas only 31% (4/13) were positive by microscopy and 42% (5/12) by culture (P < 0.05), and 87% (13/15) of those who were negative by both microscopy and culture were QFT-RD1 positive. By combining microscopy and culture with the QFT-RD1 test, sensitivity increased to 96% (CI, 90 to 102). Ten of 25 (40%) non-TB patients were QFT-RD1 positive, resulting in a specificity of 60%. However, 80% (8/10) of these had risk-factors for TB, indicating latent infection in this group. In healthy controls, only 3% (1/39) were QFT-RD1 positive. In conclusion, the QFT-RD1 test is sensitive for diagnosis of TB, especially in patients with negative microscopy and culture. The accuracy of the QFT-RD1 test will vary with the prevalence of LTBI. We suggest that the QFT-RD1 test could be a very useful supplementary tool for the diagnosis of TB.Tuberculosis (TB) remains an important and potentially fatal infection in humans, and it is estimated that one-third of the world population is infected with Mycobacterium tuberculosis (30). The most powerful tools in any TB control program are prompt diagnosis and successful treatment of patients with active contagious disease. Diagnosis of TB is often based on clinical suspicion and appropriate response to anti-TB therapy. While culture confirmation is optimal, this is frequently not possible. Detection of acid-fast bacilli or granulomatous lesions are not optimal means of diagnosing TB but are strongly indicative. The diagnosis of patients with microscopy-and culture-negative or extrapulmonary TB is complicated and is often delayed due to the need for invasive diagnostic procedures, and no definitive diagnostic test can exclude infection with M. tuberculosis. The tuberculin skin test (TST) has been used for almost a century to support the diagnosis of active and latent TB infection (LTBI) (1). The main drawback with the clinical use of the TST is the lack of specificity due to cross-reactivity with proteins present in other mycobacteria, such as the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine strain and Mycobacterium avium (1, 18). Identification and characterization of the two M. tuberculosis-specific antigens ESAT-6 and CFP...

Immigration from areas of high incidence is thought to have fueled the resurgence of tuberculosis (TB) in areas of low incidence. To reduce the risk of disease in low-incidence areas, the main countermeasure has been the screening of immigrants on arrival. This measure is based on the assumption of a prompt decline in the incidence of TB in immigrants during their first few years of residence in a country with low overall incidence. We have documented that this assumption is not true for 619 Somali immigrants reported in Denmark as having TB. The annual incidence of TB declined only gradually during the first 7 years of residence, from an initial 2,000 per 100,000 to 700 per 100,000. The decline was described by an exponential function with a half-time of 5.7 (95% confidence interval 4.0 to 9.7) years. This finding seriously challenges the adequacy of the customary practice of screening solely on arrival.