Increase in primary drug resistance of Mycobacterium tuberculosis in younger birth cohorts in France.

BACKGROUND: Monitoring of primary drug resistance is of interest for long-term evaluation of the efficacy of a national tuberculosis program. The objective was to describe changes over time in primary drug resistance among new tuberculosis patients. METHODS: Stratified analysis by birth cohorts, region of birth, HIV-coinfection of data from 14,610 culture-positive new tuberculosis patients diagnosed by a network of university hospitals between 1995 and 2008. RESULTS: Half of the patients were foreign-born, and 9% HIV-coinfected. For foreign-born and French-born patients, there was an upward trend in resistance rates to streptomycin, isoniazid, and rifampicin from the oldest to the youngest cohorts. For a same age at tuberculosis diagnosis, the risk of isoniazid resistance was higher in younger cohorts, revealing a cohort effect. Among French-born patients, the only factor independently associated with primary resistance to streptomycin, or isoniazid was birth after 1950, and particularly after 1980. Risk of streptomycin resistance increased in youngest cohorts among European-born patients. HIV-coinfection was associated to rifampicin resistance among foreign-born and French-born patients, CONCLUSIONS: Theses results indicate that among French-born patients, isoniazid-resistant strains are currently circulating in younger patients that are more likely to be infected recently, and that among foreign-born patients, HIV-coinfection is a strong risk factor for primary resistance.

Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study.

The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United Kingdom), and a widespread yet poorly defined clade (T). When the visual rules defined above were used for an automated labeling of the 813 shared types to define nine superfamilies of strains (Mycobacterium africanum, Beijing, M. bovis, EAI, CAS, T, Haarlem, X, and LAM), 96.9% of the shared types received a label, showing the potential for automated labeling of M. tuberculosis families in well-defined phylogeographical families. Intercontinental matches of shared types among eight continents and subcontinents (Africa, North America, Central America, South America, Europe, the Middle East and Central Asia, and the Far East) are analyzed and discussed.

Global distribution of Mycobacterium tuberculosis spoligotypes.

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11708 patterns from as many clinical isolates originating from more than 90 countries. The 11708 spoligotypes were clustered into 813 shared types. A total of 1300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.