Treatment of Latent Tuberculosis Infection—An Update

Huamán, Moisés A.; Sterling, Timothy R.

doi:10.1016/j.ccm.2019.07.008

Cited by 39 publications

(34 citation statements)

References 80 publications

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“…6,8,[12][13][14][15][16] There are also a clinical and an animal study which reported increased values of BMD, vitamin D and bone formation markers after treatment with LEV. 17,18 Moreover, reduced bone strength without any alteration in BMD values due to LEV treatment was also reported by Nissen-Meyer et al 19 The study of Nissen-Meyer et al reported the possibility of LEV to affect the collagen-rich matrix of bone independently from BMD without any significant change in the mineral structure. 19 The investigation of the side-effects of LEV on both bone mineral and matrix independently from each other would be helpful to reveal the different effects of the drug on bone structure.…”

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confidence: 63%

“…17,18 Moreover, reduced bone strength without any alteration in BMD values due to LEV treatment was also reported by Nissen-Meyer et al 19 The study of Nissen-Meyer et al reported the possibility of LEV to affect the collagen-rich matrix of bone independently from BMD without any significant change in the mineral structure. 19 The investigation of the side-effects of LEV on both bone mineral and matrix independently from each other would be helpful to reveal the different effects of the drug on bone structure. The exact mechanisms for possible side effects of LEV on bone tissues have not been determined yet.…”

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confidence: 63%

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The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism

Ustaoğlu¹

2020

Turkiye Klinikleri J Med Sci

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Epilepsy which affects ~1-2 % of the population worldwide is one of the most common neurodegenerative diseases. 1 In epilepsy, excessive discharge of cerebral neurons results in recurrent seizures. 2 All treatments for epilepsy aim to make the active lives of people easier by preventing further seizures while avoiding the side effects of the treatments. Primary treatment is to use anti-epileptic drugs (AEDs). How

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confidence: 63%

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confidence: 63%

The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism

Ustaoğlu¹

2020

Turkiye Klinikleri J Med Sci

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“…Latent tuberculosis infection (LTBI) is defined by the World Health Organization (WHO) as "a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active TB" (WHO, 2019). An estimated 1.8 billion people worldwide have LTBI, with wide variations in LTBI rates across countries (Houben and Dodd, 2016;Knight et al, 2019;Huaman and Sterling, 2019;Cohen et al, 2019). LTBI can be due to infection with either drug-sensitive or drugresistant M. tuberculosis (Mtb) strains.…”

Section: Introductionmentioning

confidence: 99%

Advancing new diagnostic tests for latent tuberculosis infection due to multidrug-resistant strains of Mycobacterium tuberculosis — End of the road?

Mwaba

Chakaya

Petersen

et al. 2020

International Journal of Infectious Diseases

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A B S T R A C TAn estimated 1.8 billion people worldwide have a latent tuberculosis infection (LTBI), with wide variations in LTBI rates across countries. LTBI can be due to infection with either drug-sensitive or drugresistant Mycobacterium tuberculosis (Mtb) strains. Accurate data on the prevalence of LTBI due to multidrug-resistant (MDR) Mtb strains are unavailable, since the strains cannot be isolated for resistance testing. There are no 'gold standard' tests for accurately diagnosing LTBI. Only three tests are currently available and approved by the World Health Organization (WHO) for the diagnosis of LTBI: the now outdated tuberculin skin test (TST), developed a century year ago, and the two interferon-gamma release assays (IGRAs) developed and rolled out over the past decade, the QuantiFERON (Qiagen, Germany) and T-SPOT.TB (Oxford Immunotec, United Kingdom) tests. These latter tests are not ideal due to issues of sensitivity, specificity, inability to distinguish infection with MDR-Mtb strains, and high costs. Achieving the WHO End TB Strategy target of an 80% reduction in global TB incidence by 2030 will require a major reduction in the number of persons with LTBI progressing to active TB disease. Critical to this will be the development of new diagnostic tests that are better than currently available LTBI tests at predicting who is at risk of progression to active TB disease. The diagnostic product development portfolio for LTBI appears to have reached the end of the road. Every attempt to make optimal use of currently available IGRAs using WHO LTBI guidelines for LTBI testing and treatment must be made to achieve WHO End TB strategy targets.

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“…Active TB will develop in 5-15% of individuals with LTB during their lifetimes. Several comorbidities could be related with increased risk of developing active TB, such as the HIV co-infection (Furin et al, 2019;Huaman and Sterling, 2019). Consequently, an effective treatment for LTB should be mandatory.…”

Section: Introductionmentioning

confidence: 99%

“…Current recommended LTB treatments include one of the following options: once-weekly isoniazid plus rifapentine for 3 months, daily rifampin for 4 months, daily isoniazid plus rifampin for 3-4 months, and daily isoniazid for 6-9 months (Huaman and Sterling, 2019). Treatments based on rifamycins seem to cause less adverse events and, consequently, to improve the therapy completion (Villa et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Rv0579 Is Involved in the Resistance to the TP053 Antitubercular Prodrug

et al. 2020

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Tuberculosis remains one of the leading causes of death from a single pathogen globally. It is estimated that 1/4 of the world's population harbors latent tuberculosis, but only a 5-10% of patients will develop active disease. During latent infection, Mycobacterium tuberculosis can persist unaffected by drugs for years in a non-replicating state with low metabolic activity. The rate of the successful tuberculosis treatment is curbed by the presence of these non-replicating bacilli that can resuscitate after decades and also by the spread of M. tuberculosis drug-resistant strains. International agencies, including the World Health Organization, urge the international community to combat this global health emergency. The thienopyrimidine TP053 is a promising new antitubercular lead compound highly active against both replicating and non-replicating M. tuberculosis cells, with an in vitro MIC of 0.125 µg/ml. TP053 is a prodrug activated by the reduced form of the mycothiol-dependent reductase Mrx2, encoded by Rv2466c gene. After its activation, TP053 releases nitric oxide and a highly reactive metabolite, explaining its activity also against M. tuberculosis non-replicating cells. In this work, a new mechanism of TP053 resistance was discovered. M. tuberculosis spontaneous mutants resistant to TP053 were isolated harboring the mutation L240V in Rv0579, a protein with unknown function, but without mutation in Rv2466c gene. Recombineering method demonstrated that this mutation is linked to TP053 resistance. To better characterize Rv0579, the protein was recombinantly produced in Escherichia coli and a direct interaction between the Mrx2 activated TP053 and Rv0579 was shown by an innovative target-fishing experiment based on click chemistry. Thanks to achieved results, a possible contribution of Rv0579 in M. tuberculosis RNA metabolism was hypothesized, linked to toxin antitoxin system. Overall, these data confirm the role of Rv0579 in TP053 resistance and consequently in the metabolism of this prodrug.

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Treatment of Latent Tuberculosis Infection—An Update

Cited by 39 publications

References 80 publications

The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism

The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism

Advancing new diagnostic tests for latent tuberculosis infection due to multidrug-resistant strains of Mycobacterium tuberculosis — End of the road?

Rv0579 Is Involved in the Resistance to the TP053 Antitubercular Prodrug

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