The Need for Global Action Against Multidrug-Resistant Tuberculosis

Sj, Heymann; Tf, Brewer; Me, Wilson; Hv, Fineberg

doi:10.1001/jama.281.22.2138

Cited by 26 publications

(16 citation statements)

References 11 publications

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“…Our forecasts suggest that drug-resistant TB, and particularly multidrug-resistant strains of TB, are not in the process of replacing drug-susceptible strains globally. Although TB cases are continuously emigrating from countries where the prevalence of drug resistance is high (and we have not investigated the consequences of such movement), it seems unlikely that MDR-TB, if left untreated, will`a¡ect tens of millions worldwide' (Heymann et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Will tuberculosis become resistant to all antibiotics?

Dye

Espinal

2001

Proc. R. Soc. Lond. B

123

107

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The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug e¤cacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9^64.3%), close to the 6.3% (range 0^28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1^5.9%) and 1.0% (range 0^14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative ¢tness of drug-resistant strains.

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Section: Discussionmentioning

confidence: 99%

Will tuberculosis become resistant to all antibiotics?

Dye

Espinal

2001

Proc. R. Soc. Lond. B

123

107

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“…Although use of the appropriate drug with full patient compliance is highly effective in curing pulmonary tuberculosis, the emergence of M. tuberculosis strains that are resistant to rifampin and isoniazid reduces the efficacy of standard treatment (9). This fact, and the association of tuberculosis with outbreaks (4,6,16), shows that rapid diagnosis of active tuberculosis and early detection of resistant strains are essential for effective patient management and implementation of infection control measures.…”

mentioning

confidence: 99%

Direct Detection of Rifampin- and Isoniazid-Resistant Mycobacterium tuberculosis in Auramine-Rhodamine-Positive Sputum Specimens by Real-Time PCR

et al. 2004

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Our objective was to evaluate the feasibility of a molecular assay based on a real-time PCR technique, carried out with a LightCycler instrument (Roche Biochemicals), to identify Mycobacterium tuberculosis bacilli and to detect rifampin and isoniazid resistance in DNA extracts from sputum samples. We studied three genes: rpoB, which is associated with rifampin resistance, and katG and inhA, which are associated with isoniazid resistance. A total of 205 sputum samples collected from 108 patients diagnosed with pulmonary tuberculosis with positive auramine-rhodamine-staining (AR) sputum samples, were tested. The sensitivities of the LightCycler PCR assay for the positive AR specimens was 97.5% (200 of 205) for rpoB and inhA genes and 96.5% (198 of 205) for the katG gene. For the total number of patients tested, the sensitivity was 100% (108 of 108 patients) for rifampin, whereas the sensitivity was 98.1% (106 of 108 patients) for isoniazid. Full agreement was found with the Bactec MGIT 960 method and the genotype inferred from the LightCycler data for rifampin. The phenotypic method for isoniazid reported 13 resistant strains (>0.1 g/ml). In seven (53.8%) strains there was a concordance between both methods, but we found that six (46.2%) strains reported as resistant by the phenotypic method were determined to be susceptible by real-time PCR. For the 75 strains reported as susceptible by the phenotypic method, the concordance with the LightCycler data was 100%. Our results demonstrate that rifampin-resistant M. tuberculosis could be detected in DNA extracted from auraminerhodamine-positive sputum samples in a single-tube assay that took less than 3 h to perform for a collection of auramine-rhodamine-positive specimens obtained from patients with culture-documented pulmonary tuberculosis. Similarly, this occurs in half of the isoniazid-resistant M. tuberculosis DNA extracted from auramine-rhodamine-positive specimens.

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“…An array is an orderly arrangement of samples where matching of known and unknown DNA samples is done based on base pairing rules [Heyman et al, 1999]. An array experiment makes use of common assay systems such as microplates or standard blotting membranes.…”

Section: Microarraymentioning

confidence: 99%

“…The sample spot sizes are typically less than 200 microns in diameter usually contain thousands of spots. Thousands of spotted samples known as probes (with known identity) are immobilized on a solid support (a microscope glass slides or silicon chips or nylon membrane [Heyman et al, 1999]. The spots can be DNA, cDNA, or oligonucleotides.…”

Section: Microarraymentioning

confidence: 99%