MSF Clinical Trial Reports That New Shorter Treatment Regimen Cured 89% Of Patients With Rifampin-Resistant TB

ON the 2nd day of  the 52nd Union World Conference on Lung Health (WCOLH) researchers presented data from a   study  that used  genome sequencing to effectively predict strains of tuberculosis susceptible to antibiotics that were likely to develop  drug resistance.

By Michael Gwarisa

The researchers looked at drug susceptible bacteria and aimed to identify mutations that would increase the probability of a bacteria becoming resistant in the future. The mutations confer “pre-resistance”. Monitoring these mutations could prevent the amplification of drug resistance in the population by targeting those bacteria more likely to become resistant.

There is no doubt that identifying TB strains that are likelier to become drug resistant in the future could be important for the way we treat the disease,” said Guy Marks, President of the International Union Against Tuberculosis and Lung Disease (The Union).

The Union is convenor of the World Conference. “This study is a great example of benefits of basic scientific research for the fight against serious problems like TB. It shows the potential of this work to dramatically alleviate suffering.”

“We found that isoniazid mono-resistance backgrounds have a much higher risk of acquiring further rifampicin resistance than susceptible backgrounds,” said lead author Arturo Torres Ortiz, a PHD Student at  Imperial College in the  UK.

“The most immediate application of our findings correspond to the detection of 
isoniazid mono-resistance.

“Rapid molecular tests usually focus on rifampicin resistance, which means that isoniazid mono-resistance is missed. This result in amplification into multi-drug resistance. We thus recommend that rapid molecular tests also identify regions associated to isoniazid resistance conferring mutations.”

Artificial Intelligence to read lung CT Scans

Fleming Lure, investigator at the Shenzhen Zhying Medical Imaging in Guangdong, China reported the development of AI allowing an automatic reading of DICOM CT images and then performing automatic detection of active TB.  The AI procedure can be implemented with minimal need for human intervention.

Testing children with severe pneumonia for TB in high burden TB countries

Although tuberculosis (TB) in children commonly presents as “pneumonia”, the diagnosis of TB is usually only considered if the child has a history of prolonged symptoms or fails to respond to antibiobic therapy. This leads to missed or delayed TB diagnosis. Olivier Marcy of the Bordeaux Population Health Research Center at the University of Bordeaux in France reported that his team`s study assessed the feasibility and yield of systematic evaluation for TB among children with severe pneumonia using Xpert MTB/RIF Ultra (Ultra) performed on nasopharyngeal aspirates (NPA) and stools.

TB-Speed Pneumonia was a stepped-wedge cluster-randomized trial enrolling over 1171 children aged 5 years with WHO-defined severe pneumonia in 15 hospitals from 6 high TB incidence countries (Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Uganda, and Zambia).
7.0% (82/1170) of children with severe pneumonia were diagnosed with TB in the intervention arm

A new 4-month treatment regimen for tuberculosis in adolescent participants

Persons aged 10-19 with tuberculosis (TB) account for approximately 10% of the global burden. Grace Muzanyi, Clinical Coordinator at the Uganda-Case Western Reserve University Research Collaboration in Kampala, Uganda reported on the adolescents sub-group analysis of a randomized, open-label, phase III, treatment shortening trial for pulmonary TB, compared two high-dose 4-month rifapentine regimens (with or without moxifloxacin) to the standard 6-month regimen. The study demonstrated that among adolescents  efficacy of the rifapentine-moxifloxacin regimen was similar compared to the standard regimen.

MSF clinical trial finds short, effective and safe treatment for drug-resistant tuberculosis

TB-PRACTECAL, a clinical trial led by Médecins Sans Frontières/Doctors Without Borders (MSF) has found that a new all-oral six-month treatment regimen is safer and more effective for patients with rifampicin-resistant tuberculosis (RR-TB) than the current accepted standard of care. Chief investigator Bern-Thomas Nyang’wa, Medical Director of Médecins Sans Frontières UK, noted that TB-PRACTECAL was the first-ever multi-country, randomised, controlled clinical trial to report on the efficacy and safety of a six-month, all-oral regimen for RR-TB.

The trial compared a six-month regimen including bedaquiline, pretomanid, linezolid and moxifloxacin (BPaLM) with the locally accepted standard of care. The trial enrolled 552 patients overall, of which 301 were included in the analysis at this stage. The trial took place in seven sites across Belarus, South Africa and Uzbekistan.

He reported that 89 per cent of patients in the BPaLM group were cured, compared to 52 per cent in the standard of care group.

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