Blocking TB germs’ metabolic ‘escape pathways’ may be key to better, shorter treatment

New research suggests the bacteria that cause tuberculosis alter their metabolism to combat exposure to antimicrobials, and that these metabolic “escape pathways” might be neutralized by new drugs to shorten the troublesome duration of therapy. Researchers studied the proteomic responses of the bacteria to five compounds – isoniazid, rifampicin, moxifloxacin, mefloquine and bedaquiline – and discovered escape pathways and enzymes associated with changes in metabolic state.

“When we looked at the enzymes carefully, we realized the enzymes being synthesized by the bacteria were enzymes connecting several different metabolic pathways,”Oregon State University scientist Luiz Bermudez said. “Then we came up with the idea that maybe what the bacteria were trying to do, in the presence of a bactericidal compound that was threatening their way of living, was use other ways to survive. One of the things we saw, for example, was a shift to an anaerobic metabolism, which makes a lot of drugs inactive and incapable of killing bacteria. “The gene inactivation of some of these enzymes results in improved drug efficacy against Mtb,” he said. “The identified proteins may provide powerful targets for development of synergistic drugs aimed to accelerate bacterial killing.”

Read the full statement here.

Population implications of the use of bedaquiline in people with extensively drug-resistant TB: are fears of resistance justified?

 In a Personal View published in The Lancet Infectious Diseases, Amber Kunkel, Jennifer Furin and Ted Cohen argue that resistance concerns should not forestall use of bedaquiline in patients with XDR-TB. Their position in favour of increased access to bedaquiline for these patients is based on three arguments. First, the use of drug combinations that include bedaquiline might prevent spread of XDR disease to others in the community. Second, until new combination regimens of novel drugs for XDR-TB become available, patients with XDR disease and their infected contacts will face equivalent outcomes if bedaquiline is either not provided because of policy, or not effective because of resistance. Finally, because resistance to bedaquiline and other antituberculosis drugs is caused by mutations within a single bacterial chromosome, use of bedaquiline in patients with XDR-TB will not substantially increase the risk of bedaquiline resistance in patients with drug-susceptible or multidrug-resistant (non‑XDR) tuberculosis strains.
Read the full Personal View here.

EU leaders seek new tools against drug-resistant TB

Leaders from the governments of France and the Netherlands today urged funding for new treatment and prevention tools against drug-resistant tuberculosis at a high-level meeting in Brussels, citing the scope of the problem in Europe.

“Because of drug resistance, TB is evolving to become an untreatable disease for a growing number of people,” said Michèle Boccoz, Special Ambassador for fighting against HIV/AIDS and communicable diseases at the French Ministry of Foreign Affairs and International Development. “Investment in research and development now will allow us to have the drugs and vaccines at hand to eventually end the threat of TB as a health problem in Europe.”

“Without tools such as new drugs and vaccines, we know we cannot reach our goals for controlling TB,” said Marja Esveld, senior policy advisor, global health from the Dutch Ministry of Health. “Now is the time to step up the resources to ensure we have the means to effectively end the epidemic and address the emerging threat of drug-resistant TB.”

Read the article here.

May 26th Webinar on MDR-TB treatment with BDQ in children and adolescents: experience from Belarus

DR-TB STAT and the Sentinel Project will host a webinar, MDR-TB Treatment with Bedaquiline in Children and Adolescents: Global Recommendations and Program Experience in Belarus on 26 May 2017 from 10-11am EDT.

Co-sponsored by DR-TB STAT and the Sentinel Project, this webinar will begin with an update on global guidelines for the use of new and re-purposed TB drugs by commentator Dr. Jennifer Furin. Subsequently, Dr. Skrahina will focus on interim results of bedaquiline use in the treatment of children and adolescents with multi-drug resistant tuberculosis in Belarus, including the acceptability of bedaquiline-containing regimens, culture conversion results, and the occurrence of adverse events. Dr. Skrahina and Dr. Furin will be joined by Dr. James Seddon as moderator.

For more information about the webinar and how to connect, click here.

WEBINAR SERIES: MAY 4TH, TB-PRACTECAL TRIAL

Mark your calendar for Thursday, May 4th from 08:30 to 09:30 EST (14:30-15:30 CEST, SAST) for a presentation by Dr. Bern-Thomas Nyang’wa, MD, on the TB-PRACTECAL trial

The Pragmatic Clinical Trial for More Effective Concise and Less Toxic MDR-TB Treatment Regimen(s) (TB-PRACTECAL) is a multi-center, open label, multi-arm, randomized, controlled phase II-III trial. TB-PRACTECAL, a Médecins Sans Frontières (MSF) sponsored clinical trial, aims to evaluate short treatment regimens that contain bedaquiline and pretomanid in combination with existing and re-purposed anti-TB drugs for the treatment of biologically confirmed pulmonary MDR-  and XDR-TB.  The trial’s first patient was randomized and started treatment on January 17, 2017. Additional information on the trial can be found at https://www.msf.org.uk/content/tb-practecal.

Presentation slides will be made available shortly.

TB Alliance Sublicenses Promising TB Drug from the Medicines Patent Pool

On World Tuberculosis Day, TB Alliance and the Medicines Patent Pool (MPP) announced a licensing agreement for the clinical development of sutezolid, an antibiotic drug candidate which demonstrated encouraging results in early studies. The sublicense pertains to the development of sutezolid in combination with other TB drugs and follows the MPP’s license for the treatment signed with patent holder The Johns Hopkins University in January.

Sutezolid is in the same class of drugs as linezolid (oxazolidinones), which is used in some countries as a treatment option for drug-resistant TB (DR-TB). Tests conducted over the past decade have indicated that sutezolid may have a better therapeutic potential than linezolid.

“We are grateful to the civil society coalition that pushed for the clinical development of sutezolid. If further studies are successful, this product could be a game-changer in improving options for patients” said Greg Perry, Executive Director of the Medicines Patent Pool.

To read the full article, click here.

Drug to Treat MDR-TB to be Made Available Across India

New Delhi, Apr 11: The Centre has decided to expand the availability of Bedaquiline, a drug used for treatment of drug-resistant tuberculosis, across the country.

Union Health Minister J P Nadda said that under the revised National TB Control Programme (RNTCP) in India, the drug is currently available in five cities – Ahmedabad, Delhi, Chennai, Mumbai and Guwahati.

“Based on the limited use of the drug in these five states and cities, it has been decided to expand the availability in rest of the country. Country-wide training is being carried out to build capacity of other states, and the states are also being prepared to monitor the treatment of patients with Bedaquiline containing regimen,” Nadda said.

Read the full article here.

Webinar Series: April 20th TB-CHAMP Trial

On Thursday, April 20th from 08:30 to 09:30 EST (14:30-15:30 CEST, SAST) Dr. Anneke Hesseling, MBChB, MSc, PhD, gave a presentation on the TB-CHAMP Trial

The TB-CHAMP Trial is a phase III cluster randomized, double blind, placebo-controlled, superiority multicenter trial that aims to evaluate the efficacy of levofloxacin versus placebo as preventative therapy against MDR-TB in child and adolescent household contacts.  The TB-CHAMP Trial expects to begin enrolling patients this year.

You can view the slides from Dr. Hesseling’s presentation here.

Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda

There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. This article presents the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey.

Conclusions state that there is continuity around the priorities for research in PMDT. Coordinated efforts to address questions regarding shorter treatment regimens, knowledge of disease burden without representative data, and treatment for LTBI in contacts of known DR-TB patients are essential to stem the epidemic of TB, including DR-TB.

View the full article here.

WORLD TB DAY 2017

On March 24 we commemorate World TB Day in recognition of the day in 1882 when Dr. Robert Koch announced his discovery of M. tuberculosis. While progress has been made, TB remains one of the top 10 causes of death worldwide 135 years after Dr. Koch’s discovery; in 2015, an estimated 1 million children became ill with TB, and 170,000 children died of TB. Additionally, multidrug-resistant (MDR) TB continues to become an increasingly global issue, with an estimated 480,000 people developing MDR-TB worldwide in 2015.

The theme of this year’s World TB Day is “Unite to End TB”.  Check out the links below to find out what different organizations are doing and for ways you can participate in World TB Day.

WHO World TB Day 2017

Stop TB Partnership 

CDC World TB Day in the U.S. 

Forum of International Respiratory Societies Statement for World TB Day 2017