No abstract

No abstract

Although the virulences and host ranges differ among members of theafricanum, but further characterization resulted in profiles specific for all members. Although six RD regions were used in the analyses with the original 88 isolates, it was found that the use of RD 1, RD 9, and RD 10 was sufficient for initial screenings, followed by the use of RD 3, RD 5, and RD 11 if the results for any of the first three regions were negative. When 605 sequential clinical isolates were screened, 578 (96%) were identified as M. tuberculosis, 6 (1%) were identified as M. africanum, 8 (1%) were identified as M. bovis, and 13 (2%) were identified as M. bovis BCG. Since PCR-based assays can be implemented in most clinical mycobacteriology laboratories, this approach provides a rapid and simple means for the differentiation of members of TBC, especially M. bovis and M. tuberculosis, when it is important to distinguish between zoonotic sources (i.e., cattle and unpasteurized dairy products) and human sources of tuberculosis disease.The Mycobacterium tuberculosis complex (TBC) (4, 34) comprises the closely related organisms M. tuberculosis, M. africanum, M. bovis, the M. bovis BCG vaccine strain, and two rarely seen members, M. microti and M. canettii (35). Differentiation of the members of the TBC is necessary for the treatment of individual patients and for epidemiological purposes, especially in areas of the world where tuberculosis has reached epidemic proportions or wherever the transmission of M. bovis between animals or animal products and humans is a problem. In addition, it can be important to rapidly identify isolates of M. bovis BCG recovered from immunocompromised patients.Although no clear-cut means of differentiation of the members of the TBC was found in the past by using numerical classification (34), a few conventional methods have been useful. Those methods include assays for the ability to metabolize glycerol or pyruvate in Loewenstein-Jensen medium, oxygen preference (aerophilic versus microaerophilic), niacin accumulation, nitrate reductase activity, colony morphology, and resistance to two compounds, thiophen-2-carboxylic acid hydrazide (TCH) and pyrazinamide (PZA) (12,19,38). Partially due to the slow growth of the TBC, interpretation of the results of these assays can be highly subjective, especially interpretation of differences in colony morphology (19), which can be due to the loss of virulence or to mutations associated with drug resistance. An alternative approach is the use of high-performance liquid chromatography; however, only the profile for M. bovis BCG differs from those for the other members of the complex (10).Testing for resistance to TCH has been reported to be the only single test that assigned isolates to any specific member of the TBC; classical M. tuberculosis isolates are resistant to TCH, irrespective of their resistance to isoniazid (8). Alternatively, the Asian strain of M. tuberculosis and all other members of the TBC are TCH susceptible (39, 40). However, cross-resistance to TCH has ...

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients’ skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

After start of antimicrobial treatment for Buruli ulcer, new or progressive ulceration is common before healing sets in. This paradoxical response, most prominent at the end of the 8-week antimicrobial treatment, should not be misinterpreted as failure to respond to treatment. Clinical Trials Registration. ClinicalTrials.gov, NCT00321178.