Silent Nucleotide Polymorphisms and a Phylogeny for Mycobacterium tuberculosis

Population diversity of genetically silent nucleotide polymorphisms produces a unifying phylogeny for Mycobacterium tuberculosis

Multidrug-resistant Tuberculosis Management in Resource-limited Settings

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings

Nationwide surveillance of drug-resistant tuberculosis in The Netherlands: rates, risk factors and treatment outcome

The Netherlands, 1993 and 1994. To determine 1) rates of drug resistance in relation to nationality and country of birth, 2) risk factors for drug resistance, 3) treatment outcome of drug-resistant cases, and 4) rates of primary and acquired drug resistance. Retrospective study of all cases notified with bacillary tuberculosis in The Netherlands in 1993 and 1994. Drug resistance to one or more drugs was reported in 268 (14.6%) of all 1836 cases, of whom 203 (76%) were foreign born. In Dutch patients rates of isoniazid (H) (2.9%) and streptomycin resistance (3.6%) were lower than in foreign patients (8.6% and 10.6% respectively, P < 0.001). Multidrug (H and rifampicin [R]) resistance was reported in 0.5% of Dutch-born and 1.4% of foreign cases (P = 0.055). Rates of acquired resistance to H (11.4%) and HR (5.7%) were higher than rates of primary resistance to these drugs (5.2% and 0.7% respectively, P < 0.05), but the number of retreatment cases was low (6.8% of all cases). Drug resistance was associated with immigration but not with drug use, homelessness or human immunodeficiency virus (HIV) co-infection. One fifth (20%) of drug-resistant cases was diagnosed by active case finding. Treatment outcome in sensitive and resistant cases was compared. These findings suggest that drug resistance is imported, but it is unclear to what extent drug resistance among foreigners has been transmitted or created in The Netherlands. Drug resistance data should be monitored in Dutch and foreign patients separatel

Origin and management of primary and acquired drug-resistant tuberculosis in The Netherlands: the truth behind the rates

The Netherlands, May 1994 to May 1996. 1) To estimate to what extent drug-resistant tuberculosis was acquired or recently transmitted in The Netherlands, 2) to assess the relevance of drug resistance data as routinely collected, and 3) to describe case management. Prospective descriptive study. Patients diagnosed with drug-resistant tuberculosis were interviewed. Information on patient management and contact tracing was collected. IS6110 restriction fragment length polymorphism (RFLP) patterns of all strains were compared with those of the National RFLP library and clusters were analyzed. In total 193 cases were included in the study. Acquired drug resistance (ADR) was rare. Dutch ADR patients reported receiving treatment a long time previously (mean age 58, mean treatment interval 23 years). Most foreign ADR patients had been treated recently in their country of origin. Of 151 primary drug-resistant (PDR) cases, 129 (85%) were foreign-born, of whom few (8%-19%) had been infected in The Netherlands. Few Dutch PDR cases had been infected recently (mean age 49 years). Rifampicin resistance was more frequently observed in foreign ADR cases than in foreign PDR cases (28% vs 5%; P < 0.001). One third of cases had not been treated according to treatment guidelines. Only a small proportion of drug-resistant cases resulted from recent infection or treatment in The Netherlands. General rates of ADR and PDR do not reflect current Dutch programme performance. For programme monitoring, ADR/PDR rates and their trends must be reported and evaluated in Dutch and foreign patients separatel

Preferential Deletion Events in the Direct Repeat Locus of Mycobacterium tuberculosis▿

The “Harlingen” IS6110 restriction fragment length polymorphism (RFLP) cluster has linked over 100 tuberculosis cases in The Netherlands since 1993. Four Mycobacterium tuberculosis isolates that were epidemiologically linked to this cluster had different spoligotype patterns, as well as slightly divergent IS6110 profiles, compared to the majority of the isolates. Sequencing of the direct repeat (DR) locus revealed sequence polymorphisms at the putative deletion sites. These deletion footprints provided evidence for independent deletions of the central region of the DR locus in three isolates, while the different genotype of the fourth isolate was explained by transmission. Our finding suggests that convergent deletions in the DR locus occur frequently. However, deletion footprints are not suitable to detect convergent deletions in the DR because they seem to be exceptional. Deletion footprints in the DR were not described previously, and we did not observe them in any public M. tuberculosis complex sequences. We conclude that preferential deletions in the DR loci of closely related strains are usually an unnoted event that interferes with clustering of closely related strains