High Rate of Tuberculosis Reinfection during a Nosocomial Outbreak of Multidrug-Resistant Tuberculosis Caused by Mycobacterium bovis Strain B

Rivero, Antonio; Márquez, Manuel; Santos, Jesús; Pinedo, A; Sánchez, María Antonia Huertas; Esteve, Adela; Samper, Sofía; Martı́n, Carlos

doi:10.1086/317547

Cited by 100 publications

(75 citation statements)

References 6 publications

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“…61 The PhoR protein is a transmembrane histidine kinase that transmits signals from the environment. Autophosphorylation of PhoR is followed by transfer of the phosphoryl group to PhoP, a response regulator that mediates expression of multiple genes, 62 including genes for the biosynthesis of trehalose-containing cell wall lipids [63][64][65] and ESX-1 secretion. 66 A role for phoP in virulence of the M. tb complex was first suggested during a severe nosocomial outbreak of multidrug resistant TB in humans in Spain.…”

Section: Correlation With Residual Virulence and Reactogenicitymentioning

confidence: 99%

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

Liu

Tran²,

Leung³

et al. 2009

Human Vaccines

123

117

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by MDR strains that are also resistant to a fluoroquinolone and at least one second-line injectable agent (amikacin, kanamycin and/or capreomycin), caught the world's attention after an outbreak in KwaZulu-Natal, South Africa, where 52 of 53 infected patients died. 2 HIV co-infection was a contributing factor in most of these deaths, and indeed, a deadly association between HIV and TB has been known almost since the start of the HIV-epidemic. Of the 1.7 million people who died from TB in 2006, an estimated 200,000 were co-infected with HIV. 1 Because of these situations, effective approaches alternative to antibiotics are urgently needed for the control of TB.Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis (M. bovis), is currently the only available vaccine against TB. Since 1974, BCG vaccination has been included in the WHO Expanded Program on Immunization. 3 It is estimated that more than 3 billion individuals have been immunized with BCG and over 100 million doses of BCG are administered annually, making it the most widely used vaccine in humans. 3 Meta-analysis studies have confirmed that BCG protects children, providing >80% efficacy against severe forms of TB, including tuberculous meningitis and miliary TB. 4,5 In contrast, evidence for protection against pulmonary TB in adolescents and adults remains contentious as efficacy estimates from clinical trials, observational case control studies and contact studies range from 0 to 80%. 6,7 The reasons for the variable protective efficacy are unknown but several hypotheses have been proposed, including differences among the vaccine strains used in clinical studies, exposure of trial populations to environmental mycobacteria, nutritional or genetic differences in human populations, differences in trial methods, and variations among clinical M. tb strains. 8-13 These explanations are not mutually exclusive and all may contribute to the heterogeneity in vaccine efficacy.A key aspect of this issue may concern the nature of BCG attenuation. Although it is generally considered safe and has been used as a human vaccine since the 1920s, the mechanisms of BCG attenuation remain largely unknown. This is further complicated by the fact that BCG is not a single strain, but instead comprises a number of substrains that exhibit phenotypic and biochemical differences. 14 BCG strains also exhibit differences in residual virulence level. [15][16][17] However, side effects were often attributed to variations in the viability of vaccines during preparation procedures (e.g., freezedrying). 14 In other words, the observed differential virulence among Mycobacterium bovis Bacille Calmette-Guérin (BCG) was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, the mechanisms of attenuation of BCG remain poorly understood. BCG is not a single organism, but comprises a number of substrains that differ in genotypes and phenotypes. The impacts of these differences on BCG...

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Section: Correlation With Residual Virulence and Reactogenicitymentioning

confidence: 99%

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

Liu

Tran²,

Leung³

et al. 2009

Human Vaccines

123

117

View full text Add to dashboard Cite

show abstract

“…Reinfection of patients on therapy for drugsensitive disease has been described in several different high-incidence settings and has been associated with nosocomial transmission. [27][28][29][30][31] Usually, MDR-TB patients in the Russian Federation are not placed on respiratory precautions in the hospitals or clinics where they receive care, so there is opportunity for further spread of drug-resistant strains among patients receiving therapy for drug-sensitive disease. The finding that substance abuse was a risk factor for late occurrence of MDR also raises the possibility that these patients are at higher risk of exposure to drug-resistant disease or are more susceptible to reinfection than other patients.…”

Section: Researchmentioning

confidence: 99%

Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance

Iy¹,

Keshavjee

et al. 2007

Bull World Health Organ

141

112

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Objective To identify barriers to successful tuberculosis (TB) treatment in Tomsk, Siberia, by analysing individual and programmatic risk factors for non-adherence, default and the acquisition of multidrug resistance in a TB treatment cohort in the Russian Federation. Methods We conducted a retrospective cohort study of consecutively enrolled, newly detected, smear and/or culture-positive adult TB patients initiating therapy in a DOTS programme in Tomsk between 1 January and 31 December 2001. Findings Substance abuse was strongly associated with non-adherence [adjusted odds ratio (OR): 7.3; 95% confidence interval (CI): 2.89-18.46] and with default (adjusted OR: 11.2; 95% CI: 2.55-49.17). Although non-adherence was associated with poor treatment outcomes (OR: 2.4; 95% CI: 1.1-5.5), it was not associated with the acquisition of multi-drug resistance during the course of therapy. Patients who began treatment in the hospital setting or who were hospitalized later during their treatment course had a substantially higher risk of developing multidrug-resistant TB than those who were treated as outpatients (adjusted HRs: 6.34; 95% CI: 1.35-29.72 and 6.26; 95% CI: 1.02-38.35 respectively). Conclusion In this cohort of Russian TB patients, substance abuse was a strong predictor of non-adherence and default. DOTS programmes may benefit from incorporating measures to diagnose and treat alcohol misuse within the medical management of patients undergoing TB therapy. Multidrug-resistant TB occurred among adherent patients who had been hospitalized in the course of their therapy. This raises the possibility that treatment for drug-sensitive disease unmasked a pre-existing population of drugresistant organisms, or that these patients were reinfected with a drug-resistant strain of TB.

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“…The criteria used for the differentiation of Mycobacterium tuberculosis and M. bovis have been colony morphology, nitrate reduction, niacin test, and sensitivity or resistance to pyrazinamide. Deviations from standard patterns in all of the above tests have been reported, making it virtually impossible to differentiate between M. bovis, M. tuberculosis, and M. africanum (12,34,38,48). The high degree of variability in the phenotypic characteristics has made it important to develop reliable techniques to distinguish between members of the Mycobacterium tuberculosis and M. bovis (MTB) complex (22,41).…”

mentioning

confidence: 99%

Use of the hupB Gene Encoding a Histone-Like Protein of Mycobacterium tuberculosis as a Target for Detection and Differentiation of M. tuberculosis and M. bovis

et al. 2004

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The gene for histone-like protein (hupB [Rv2986c]) of Mycobacterium tuberculosis has been identified as a singular target which allows differentiation of two closely related mycobacterial species, namely, M. tuberculosis and M. bovis of the MTB complex, by a PCR assay. The N and S primer-generated PCR amplicons differed in M. tuberculosis and M. bovis; these amplicons were determined to be 645 and 618 bp, respectively. This difference was localized to the C-terminal part of the gene by using primers M and S. The C-terminal PCR amplicons of M. tuberculosis and M. bovis were determined to be 318 and 291 bp, respectively. The differences in the C-terminal portion of the gene were confirmed by restriction fragment length polymorphism analysis and sequencing. Sequence analysis indicated that in M. bovis there was a deletion of 27 bp (9 amino acids) in frame after codon 128 in the C-terminal part of the hupB gene. In the present study 104 mycobacterial strains and 11 nonmycobacterial species were analyzed for hupB gene sequences. Of the 104 mycobacterial strains included, 62 belonged to the MTB complex and 42 were non-MTB complex strains and species. Neither the hupB gene-specific primers (N and S) nor the C-terminal primers (M and S) amplify DNA from any other mycobacteria, making the assay suitable for distinguishing members of the MTB complex from other mycobacterial species, as well as for differentiating between members of the MTB complex, namely, M. tuberculosis and M. bovis.Early and reliable detection of pathogenic mycobacteria in clinical samples is a major limitation in the control of human tuberculosis. At present, a battery of tedious tests (microbiological, biochemical, etc.) requiring more than several days or weeks are routinely used to identify clinical mycobacterial isolates. The criteria used for the differentiation of Mycobacterium tuberculosis and M. bovis have been colony morphology, nitrate reduction, niacin test, and sensitivity or resistance to pyrazinamide. Deviations from standard patterns in all of the above tests have been reported, making it virtually impossible to differentiate between M. bovis, M. tuberculosis, and M. africanum (12, 34, 38, 48). The high degree of variability in the phenotypic characteristics has made it important to develop reliable techniques to distinguish between members of the Mycobacterium tuberculosis and M. bovis (MTB) complex (22,41). Techniques based on the amplification of mycobacterial DNA sequences by PCR have been introduced in many laboratories as a promising alternative rapid, sensitive, and specific detection of M. tuberculosis in clinical specimens (2,7,14).Novel targets have been exploited for diagnostic purposes by using PCR, namely, the devR response regulator gene (42, 43), rRNA (5), selected chromosomal fragments (3,18,25,29), genes coding for the 65-kDa heat shock protein (36), the 38-kDa protein antigen (44), the dnaJ gene (47), and insertion sequences such as IS6110, IS990, and IS1081 (1,15,16,23); these are all examples of diverse targets that ...

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High Rate of Tuberculosis Reinfection during a Nosocomial Outbreak of Multidrug-Resistant Tuberculosis Caused by Mycobacterium bovis Strain B

Cited by 100 publications

References 6 publications

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

BCG Vaccines: Their mechanisms of attenuation and impact on safety and protective efficacy

Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance

Use of the hupB Gene Encoding a Histone-Like Protein of Mycobacterium tuberculosis as a Target for Detection and Differentiation of M. tuberculosis and M. bovis

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