Analysis of an interferon-gamma release assay for monitoring the efficacy of anti-tuberculosis chemotherapy.

The reported effect of anti-tuberculosis chemotherapy on interferon-gamma (IFN-γ) release in response to specific Mycobacterium tuberculosis antigens has been inconsistent. The objective of this study was therefore to determine the effect of anti-tuberculosis chemotherapy on IFN-γ response to ESAT-6 and CFP-10. QuantiFERON®-TB Gold (QFT-G) was performed, and the IFN-γ response to ESAT-6 and CFP-10 were measured, for 50 people with culture-confirmed tuberculosis prior to initiating treatment and periodically for up to 120 weeks following initiation of said treatment. IFN-γ responses and bacteriological response were compared. The average IFN-γ response to ESAT-6 and CFP-10 and the proportion of QFT-G results that were positive decreased during chemotherapy and for several weeks thereafter, reaching lows at weeks 48 to 56. Furthermore, these measures were lower at 48 weeks for those with bacteriological reversion prior to the second monthly visit than for those with slower reversion. Although it was shown that anti-tuberculosis treatment generally reduced the specific release of IFN-γ, the effect is so variable that it could be used as a monitor of progress of chemotherapy with great care and reservation.

Functional and evolutionary genomics of Mycobacterium tuberculosis: insights from genomic deletions in 100 strains.

To better understand genome function and evolution in Mycobacterium tuberculosis, the genomes of 100 epidemiologically well characterized clinical isolates were interrogated by DNA microarrays and sequencing. We identified 68 different large-sequence polymorphisms (comprising 186,137 bp, or 4.2% of the genome) that are present in H37Rv, but absent from one or more clinical isolates. A total of 224 genes (5.5%), including genes in all major functional categories, were found to be partially or completely deleted. Deletions are not distributed randomly throughout the genome but instead tend to be aggregated. The distinct deletions in some aggregations appear in closely related isolates, suggesting a genomically disruptive process specific to an individual mycobacterial lineage. Other genomic aggregations include distinct deletions that appear in phylogenetically unrelated isolates, suggesting that a genomic region is vulnerable throughout the species. Although the deletions identified here are evidently inessential to the causation of disease (they are found in active clinical cases), their frequency spectrum suggests that most are weakly deleterious to the pathogen. For some deletions, short-term evolutionary pressure due to the host immune system or antibiotics may favor the elimination of genes, whereas longer-term physiological requirements maintain the genes in the population.

[Process of acquiring drug resistance: retrospective review of records of MDR TB].

PURPOSE: To investigate the reasons of acquiring drug resistance among MDR TB cases and to learn lessons for the prevention of acquiring of drug resistance. METHOD: Retrospective review of 159 MDR TB cases who were treated at Fukujuji Hospital from 1990 January to 2003 August. RESULT: We found that among 159 cases, 48 cases were infected with multidrug resistant M. tuberculosis bacilli, 35 cases acquired drug resistance, 7 cases were with the history of tuberculosis treatment before 1970 only, and that remaining 69 cases were difficult to evaluate because of the lack of informations on previous drug susceptibility tests. Among 35 cases that acquired drug resistance, the drug susceptibility test patterns before becoming MDR TB were categorized as follows: 12 HR susceptible, 18 H resistant R susceptible, 3 R susceptible (H unknown), and 2 H susceptible R resistant. The factors that may have influenced to acquire MDR were lack of modification of the regimen after knowing drug resistance among H resistant R susceptible cases, and defaulting among cases that were not evaluated (15/69) and H resistant R susceptible cases (3/18). DISCUSSION: Control of MDR TB needs to be strengthened. Proper drug susceptibility test, proper choice of drugs at the beginning of treatment and modification of treatment after knowing drug susceptibility test results are important for the prevention of MDR TB. Ensuring patient adherence to treatment is important in the medical institutions where drug susceptibility test is not properly done, in particular, for H resistant R susceptible cases, and guidance to these institutions by the public health centers should be intensified.