We used direct repeat (DR)-based spacer oligonucleotide typing (spoligotyping) (in association with double-repetitive element–polymerase chain reaction, IS6110-restriction fragment length polymorphism [RFLP], and sometimes DR-RFLP and polymorphic GC-rich sequence-RFLP) to detect epidemiologic links and transmission patterns of Mycobacterium tuberculosis on Martinique, Guadeloupe, and French Guiana. In more than a third of the 218 strains we typed from this region, clusters and isolates shared genetic identity, which suggests epidemiologic links. However, because of limited epidemiologic information, only 14.2% of the strains could be directly linked. When spoligotyping patterns shared by two or more isolates were pooled with 392 spoligotypes from other parts of the world, new matches were detected, which suggests imported transmission. Persisting foci of endemic disease and increased active transmission due to high population flux and HIV-coinfection may be linked to the recent reemergence of tuberculosis in the Caribbean. We also found that several distinct families of spoligotypes are overrepresented in this region.
The recent upsurge in the incidence of tuberculosis with significant emergence of multidrug-resistant cases has focused on the priority of discovering effective new drugs and on the strategies to augment the potential of existing drugs against Mycobacterium tuberculosis. In the present study, we investigated cerulenin and trans-cinnamic acid, which have recently been shown to augment the activity of various antibiotics against Mycobacterium avium [Antimicrob. Agents Chemother. 38 (1994) 2287-2295], to enhance the activity of isoniazid, rifampin, ofloxacin, amikacin and clofazimine against M. tuberculosis. The synergy observed was compared with identical combinations using ethambutol, a cell wall-inhibiting drug used in standard antituberculous chemotherapy. The results showed that ethambutol resulted in synergistic activity in 12/30 drug combinations, as compared to 15/36 for cerulenin and 101/18 for trans-cinnamic acid. This increase in drug activity was even observed with drug-resistant isolates. Use of novel antimicrobials and understanding of their mechanisms of action may be an effective strategy to determine previously undescribed targets for future drug development.
Because of a substantial increase in human immunodeficiency virus (HIV) infection and HIV-linked tuberculosis in the Caribbean, a molecular fingerprinting study of clinical isolates of Mycobacterium tuberculosis isolated at the Pasteur Institute of Guadeloupe from 1994 to 1995 was undertaken with the insertion sequence IS6110 and the direct repeat DRr probes. We present the results for 72 isolates from 51 patients. A major cluster (cluster A) representing isolates from 12 patients (24%) was detected upon PvuII-IS6110 fingerprinting, which revealed a pattern of four bands among these isolates. Homogeneity was retained when the isolates were further analyzed with the DRr probe or further characterized by AluI and SmaI-DRr restriction fragment length polymorphism analysis. The isolates of cluster A, from 10 men and 2 women, was present in people of all ages and of different ethnic and geographical backgrounds, and infection with these isolates was independent of the HIV status of the patients (except for 2 HIV-positive patients from the same ward from whom the tubercle bacilli were isolated at the same time). The percentage of reactivation versus active transmission events could not be precisely determined in this study. These results are discussed on the basis of the genetic advantage of predominant clusters and/or specific characteristics of the settings from which a similar cluster of isolates with four bands has so far been reported, which include South Africa, French Polynesia, and Guadeloupe.
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