- Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI. [Journal Article]
- JCJ Clin Med 2019 Jun 06; 8(6)
- CONCLUSIONS: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.
- Completion Rates, Adverse Effects, and Costs of a 3-Month and 9-Month Treatment Regimen for Latent Tuberculosis Infection in California Inmates, 2011-2014. [Journal Article]
- PHPublic Health Rep 2019 May/Jun; 134(1_suppl):71S-79S
- CONCLUSIONS: In an incarcerated population, the 3HP regimen had a higher completion rate, lower hepatotoxicity, and lower cost per fully treated patient than the 9H regimen. If coupled with a high treatment initiation rate, the high rate of LTBI treatment completion with 3HP may contribute to reducing tuberculosis morbidity in California.
- Shortening Buruli ulcer treatment with combination therapy targeting the respiratory chain and exploiting M. ulcerans gene decay. [Journal Article]
- AAAntimicrob Agents Chemother 2019 Apr 29
- Buruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients. However, STR requires injections and m…
Buruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients. However, STR requires injections and may be toxic and CLR shares an adverse drug-drug interaction with RIF and may be poorly tolerated. Studies in a mouse footpad infection model showed that increasing the dose of RIF or using the long-acting rifamycin, rifapentine (RPT), in combination with clofazimine (CFZ), a relatively well-tolerated antibiotic, can shorten treatment to 4 weeks. CFZ is reduced by a component of the electron transport chain (ETC) to produce reactive oxygen species toxic to bacteria. Synergistic activity of CFZ with other ETC-targeting drugs, the ATP synthase inhibitor bedaquiline (BDQ) and the bc1:aa3 oxidase inhibitor Q203 (now named Telacebec), was recently described against Mycobacterium tuberculosis Recognizing that M. tuberculosis mutants lacking the alternative bd oxidase are hyper-susceptible to Q203 and that Mycobacterium ulcerans is a natural bd oxidase-deficient mutant, we tested the in vitro susceptibility of M. ulcerans to Q203 and evaluated the treatment-shortening potential of novel 3- and 4-drug regimens combining RPT, CFZ, Q203 and BDQ in a mouse footpad model. The MIC of Q203 was extremely low (0.000075 - 0.00015 μg/ml). Footpad swelling decreased more rapidly in mice treated with Q203-containing regimens compared to RIF+STR and RPT+CFZ. Nearly all footpads were culture-negative after only 2 weeks of treatment with regimens containing RPT, CFZ, and Q203. No relapse was detected after only 2 weeks of treatment in mice treated with any of the Q203-containing regimens. In contrast, 15% of mice receiving RIF+STR for 4 weeks relapsed. We conclude that it may be possible to cure patients with Buruli ulcer in 14 days or less using Q203-containing regimens rather than currently recommended 56-day regimens.
- Controlling latent TB tuberculosis infection in high-burden countries: A neglected strategy to end TB. [Journal Article]
- PMPLoS Med 2019; 16(4):e1002787
- In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infecti…
In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.
- Addressing tuberculosis among Inuit in Canada. [Journal Article]
- CCCan Commun Dis Rep 2018 Mar 01; 44(3-4):82-85
- The average annual rate of tuberculosis (TB) among Inuit in Canada is now more than 290 times higher than Canadian born non-Indigenous people. How did this happen? Using the Territory of Nunavut as a…
The average annual rate of tuberculosis (TB) among Inuit in Canada is now more than 290 times higher than Canadian born non-Indigenous people. How did this happen? Using the Territory of Nunavut as a case example, the roots of this situation can largely be traced back to social determinants of health and challenges in access to health care. Half (52%) of all Nunavut residents live in social housing, often under overcrowded conditions. Many experience food insecurity, with food prices in Nunavut that are twice those in southern Canada. Sixty percent of Nunavut residents smoke. Challenges in health care delivery include the small isolated communities, with few roads and difficult weather conditions during the long winters, which impede the ability to reach or provide healthcare, staff that arrive with little TB experience or cultural knowledge, multiple competing health care demands, limited resources and high staff turnover. The housing shortage is not only a social determinant of health, it also impacts the ability to hire new staff or mount an effective response in the event of an outbreak. Yet despite these challenges, progress has been made. Tuberculosis care in Nunavut includes active case finding, contact tracing for all cases of infectious TB, and screening of school age children. Rapid testing with the GeneXpert© platform has resulted in a quicker diagnosis of active TB, earlier treatment (preventing progression of disease) and less transmission. Progressively, there has been a switch from plain film to digital x-rays reducing x-ray turnaround time from as long as two to three weeks to one or two days. Standard treatment protocols include quadruple therapy until sensitivities are known, the use of home isolation for active cases and directly observed treatment (DOT) for both latent and active TB. Special access to rifapentine (Priftin), and its use in combination therapy (3HP), requires only once weekly treatments that can be completed in 12 visits instead of 78 visits for isoniazid (INH) or 120 visits for rifampin, which increases adherence and greatly reduces the health care resources needed to treat TB. In October 2017, the Honourable Jane Philpott, then Minister of Health and now Minister of Indigenous Services, and Natan Obed, president of Inuit Tapiriit Kanatami (ITK) announced the establishment of a Task Force to develop an Inuit TB Elimination Action Framework, accompanied by regional action plans. It is hoped that the task force, and current efforts in Nunavut, will lead to the long term changes needed to ultimately eliminate TB among Inuit in Canada.
- Outlook for tuberculosis elimination in California: An individual-based stochastic model. [Journal Article]
- PlosPLoS One 2019; 14(4):e0214532
- CONCLUSIONS: Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks.
- Treatment-Shortening Effect of a Novel Regimen Combining Clofazimine and High-Dose Rifapentine in Pathologically Distinct Mouse Models of Tuberculosis. [Journal Article]
- AAAntimicrob Agents Chemother 2019; 63(6)
- Clofazimine and high-dose rifapentine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both mo…
Clofazimine and high-dose rifapentine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.
- Tuberculosis. [Review]
- LctLancet 2019 Apr 20; 393(10181):1642-1656
- Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. Advances in diagno…
Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. Advances in diagnosis, including the use of rapid molecular testing and whole-genome sequencing in both sputum and non-sputum samples, could change this situation. Although little has changed in the treatment of drug-susceptible tuberculosis, data on increased efficacy with new and repurposed drugs have led WHO to recommend all-oral therapy for drug-resistant tuberculosis for the first time ever in 2018. Studies have shown that shorter latent tuberculosis prevention regimens containing rifampicin or rifapentine are as effective as longer, isoniazid-based regimens, and there is a promising vaccine candidate to prevent the progression of infection to the disease. But new tools alone are not sufficient. Advances must be made in providing high-quality, people-centred care for tuberculosis. Renewed political will, coupled with improved access to quality care, could relegate the morbidity, mortality, and stigma long associated with tuberculosis, to the past.
- Facile in situ generation of bismuth tungstate nanosheet-multiwalled carbon nanotube composite as unconventional affinity material for quartz crystal microbalance detection of antibiotics. [Journal Article]
- JHJ Hazard Mater 2019 Jul 05; 373:50-59
- Overuse and thus a constant presence of antibiotics leads to various environmental hazards and health risks. Thus, accurate sensors are required to determine their presence. In this work, we present …
Overuse and thus a constant presence of antibiotics leads to various environmental hazards and health risks. Thus, accurate sensors are required to determine their presence. In this work, we present a mass-sensitive sensor for the detection of rifampicin. We chose this molecule as it is an important antibiotic for tuberculosis, one of the leading causes of deaths worldwide. Herein, we have prepared a carbon nanotube reinforced with bismuth tungstate nanocomposite material in a well-defined nanosheet morphology using a facile in situ synthesis mechanism. Morphological characterization revealed the presence of bismuth tungstate in the form of square nanosheets embedded in the intricate network of carbon nanotubes, resulting in higher surface roughness of the nanocomposite. The synergy of the composite, so formed, manifested a high affinity for rifampicin as compared to the individual components of the composite. The developed sensor possessed a high sensitivity toward rifampicin with a detection limit of 0.16 μM and excellent specificity, as compared to rifabutin and rifapentine. Furthermore, the sensor yielded statistically good recoveries for the monitoring of rifampicin in human urine samples. This work opens up a new horizon for the exploration of unconventional nanomaterials bearing different morphologies for the detection of pharmaceuticals.
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- Tolerability of rifapentine-based regimens in latent tuberculosis infection treatment in the elderly. [Letter]
- EREur Respir J 2019; 53(3)