The Union World Conference on Lung Health 2023 - Wednesday 15 November press release
- Research breakthroughs presented at The Union World Conference for Lung Health include new drug regimens to treat multidrug-resistant tuberculosis, cutting treatment time by over 60%;
- MDR-TB current affects half a million people each year, with treatment requiring up to 14,000 pills;
- World’s first estimates of the deadliest form of childhood TB revealed;
- First multi-country research finds new BPaL treatment is ‘highly effective’;
- Asymptomatic TB has a similar danger to symptomatic counterpart
What the press conference on YouTube.
Paris; November 15th 2023: Leading experts in tuberculosis (TB) have discovered four new, improved regimens to treat drug resistant tuberculosis that could cut treatment time by over 60%.
On the opening day of the Union World Conference, three regimens were found to have achieved favourable outcomes between 85-90% of participants for treating multidrug-resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB).
Research led by Médecins Sans Frontières, Partners in Health, and Interactive Research and Development, found that a further fourth regimen showed a strong treatment response at 85.6% and represented an alternative for people who cannot tolerate bedaquiline or linezolid.
These drug regimens for MDR/RR-TB represent similar efficacy and safety to conventional treatments, but reduced treatment time by up to two-thirds.
Roughly half a million people fall sick with MDR/RR-TB each year, and many die from it.
Many living with TB face treatments that last up to 24 months. Such regimens can be ineffective, with only 59% treatment success in 2018, and can often cause terrible side effects. Patients on these regimens must ingest up to 14,000 pills over the full course of treatment, and some have to endure months of painful, daily injections.
Over 750 participants from 11 sites, 7 countries, and 4 continents were involved in the study funded by Unitaid into tackling MDR/RR-TB.
The trial showed how combining antibiotics in new ways could treat this form of the disease more effectively than ever before, offering hope for those suffering from this fatal condition.
Dr Carole Mitnick, Professor of Global Health and Social Medicine at Harvard Medical School and Partners in Health Director of Research for the endTB project, said: “We stand on the cusp of a significant breakthrough in the battle against MDR, a disease that disproportionately affects impoverished populations around the globe. Our results offer hope to those in dire need and underscore the urgency of continued research and innovation—and accountability of private companies that receive public funds—to address diseases that too often strike the most vulnerable among us.”
The researchers’ findings are a significant step and could address issues around access to and affordability of quality TB care.
FIRST GLOBAL ESTIMATES OF DEVASTATING FORM OF CHILDHOOD TUBERCULOSIS
At The Union World Conference on Lung Health a global group of research, led by Stellenbosch University, presented the world’s first estimates of childhood tuberculous meningitis (TBM), discovering over 20,000 children developing TBM in 2019.
Amongst children with TBM, nearly 15,000 children died from TBM, leading to researchers to suggest that owing to the high mortality and morbidity rates, this is the most devastating form of childhood TB.
The study also found that lack of access to TB treatment was a key contributor to the high mortality rate, with over 80% of children who died from the disease not receiving TB treatment – the majority younger than 5 years of age.
TBM is fatal if untreated and can cause life-long disability in survivors. To date, research has focused on clinical management and outcomes. However, there is a paucity of research on the burden and impact of this devastating disease, including how many children are affected.
The study quantified the global number of children developing TBM, dying of TBM and suffering neurological sequalae following TBM in 2019.
Lead scientist Dr Karen Du Preez, Department of Paediatrics and Child Health at Stellenbosch University said: “If TBM is diagnosed early in the course of disease, the outcomes are much better. Many cases can also be prevented. Public health programs in high TB burden countries should start reporting all diagnosed cases of TBM in children, as this is the first step towards improving health systems for affected children and their families.”
Researchers recommended strategies to facilitate early diagnosis and TBM prevention, such as BCG vaccination and TB preventive therapy, should be prioritised and expanded henceforth.
NEW DRUG-RESISTANT TB TREATMENT SHOWS “HIGHLY EFFECTIVE” RESULTS IN REAL-WORLD SETTINGS
A global study, developed by TB Alliance known as LIFT-TB, into pilot of six-month, all-oral treatment regimen to accelerate its implementation and rollout in Central and Southeast Asia has been found to be ‘highly effective’ .
The three-drug regimen, known as BPaL (comprised of bedaquiline, pretomanid, and linezolid) showed a 94.5% cure rate across five of the LIFT-TB countries.
The global treatment success rate of drug-resistant TB (DR-TB) was about 63% prior to the uptake of new regimens, according to the World Health Organization 2023 Global TB Report.
The BPaL regimen reduces the length of treatment for DR-TB from 18 months or longer, to six months, and projects to be more cost-effective than previous therapies, which can help reduce some of the burden on people with DR-TB, caregivers, and health systems.
Sandeep Juneja, Senior Vice President of Market Access at TB Alliance said: “This example will help drive wider and faster uptake of BPaL. By acting quickly, other countries and national TB programs can help save many lives.”
DANGERS OF ASYMPTOMATIC TB DISCOVERED
A team of scientists, led by the Africa Health Research Institute, has highlighted that asymptomatic TB has a similar bacterial burden and frequency of drug resistance as symptomatic TB.
Asymptomatic TB makes up half of TB cases globally and was previously missed by other testing technologies, such as Xpert.
These findings demonstrate that there is a significant reservoir of drug-resistant TB which is unlikely to be detected by current, passive case-finding strategies.
The team conducted a community-based survey between 2018 and 2020 to identify the presence of infectious diseases in rural KwaZulu-Natal, in South Africa.
Where people in the community reported any of the four World Health Organisation TB screening symptoms – which are coughing, fever, night sweats, or weight loss – or had abnormal chest X-rays, the researchers collected spit samples for testing.
Dr Emily Wong, study lead and faculty member at Africa Health Research Institute: "These findings highlight a critical gap in our current approach to TB detection. The substantial burden of drug-resistant TB among individuals with subclinical cases especially emphasises the need for new, proactive and scalable strategies to identify asymptomatic TB.”
The Union World Conference on Lung Health is convened by the International Union Against Tuberculosis and Lung Disease, the world’s first global health organisation, committed to eradicating tuberculosis and lung disease.
All these scientific discoveries come at a crucial moment for the TB community after world leaders pledged funding and agreed targets for the next five years towards ending the global TB epidemic at UN High-Level meeting on health in New York in September.
Professor Guy B. Marks, President and (Interim) Executive Director, International Union Against Tuberculosis and Lung Disease (The Union) said: “The Union World Conference on Lung Health has kicked off with the most exciting minds from across the TB community coming together to share their pioneering research. The Union is proud to support these researchers’ vitally important work and help to provide solutions to what we consider to be the most prominent global health threat.”
Established in 1920 as the world’s first global health organisation the International Union Against Tuberculosis and Lung Disease is committed to eradicating tuberculosis and lung disease, leading to a healthier world for all. Its members, staff, and consultants work in more than 140 countries globally.
The Union aims to improve the world’s lung health by prioritising prevention and care, through bringing together clinicians, patients, survivors, policy makers, scientists, and managers to disseminate and implement knowledge in practice. The Union’s work is exemplified by its core values of quality, transparency, accountability, respect, and independence.
Notes to editors:
This is a press release issued by Lexington on behalf of the International Union Against Tuberculosis and Lung Disease. For more information, please contact firstname.lastname@example.org. You can find more press releases from The Union here.
To attend a virtual press conference with the authors of these scientific articles and Guy B. Marks, President of The Union, please register to join here. This will be live streamed here. This will be taking place at 13:30 CET, 15th November 2023.
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Overview of Abstracts:
Safety and effectiveness of the BPaL regimen: preliminary analysis of the first multi-country operational research cohort.
- Summary: WHO recommends programmatic scaling-up of BPaL for pre-XDR-TB treatment. Operational Research in Indonesia, Kyrgyzstan, the Philippines, Uzbekistan, and Viet Nam will provide essential supplementary evidence in establishing the safety and effectiveness of BPaL usage under programmatic conditions.
- Design/Methods: Indonesia, Kyrgyzstan, the Philippines, Uzbekistan, and Viet Nam introduced the BPaL regimen under OR conditions. Between May 2021 and March 2023, 319 individuals with multidrug- or rifampicin-resistant (MDR/RR-) TB with treatment intolerance, non-response, or additional fluoroquinolones resistance (pre-XDR-TB) were enrolled in the OR. The findings of this multi-country OR will serve as essential supplementary evidence in establishing the safety and effectiveness of BPaL usage under programmatic conditions.
- Results: The OR cohort had a median age of 40 years (IQR: 29-52), with 187 males (58.6%) out of the total. At baseline, 176 individuals (55.2%) were culture positive, and 158 individuals (89.8%) reported no growth in MGIT culture after one month of BPaL treatment. End-of-treatment outcomes were available for 146 individuals (45.8%) as of February 2023, and 138 individuals (94.5%) completed BPaL treatment successfully. Of these, 88 individuals (60.3%) reported adverse events of special interest that led to discontinuation or interruption of the full BPaL regimen or Linezolid only or permanent dose reduction of Linezolid in BPaL. Two individuals (1.4%) were classified as treatment failures due to BPaL discontinuation. Table 1 summarizes the effectiveness and safety of the BPaL regimen.
Innovation to guide practice in MDR/RR-TB treatment: efficacy and safety results of the endTB trial
- Summary: Results presented for the first time today at the Union World Conference on Lung Health revealed evidence to support the use of four new, improved regimens to treat multi-drug resistant tuberculosis or rifampicin-resistant tuberculosis (MDR/RR-TB). The endTB trial enrolled a diverse group of 754 patients from seven countries (Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa).
- Results: The endTB clinical trial evaluated five experimental regimens for MDR/RR-TB against the standard of care in two distinct analysis populations. endTB regimens 1, 2, 3, demonstrated non-inferiority to the control in both primary analysis populations, establishing their success in treating RR-TB. Regimens 1, 2, and 3 achieved favorable outcomes in 89.0%, 90.4%, and 85.2% of participants, respectively. Regimen 5 also showed a strong treatment response at 85.6% and was non-inferior to the control's 80.7% in one of the primary analysis populations. While consistent results in both populations are needed to formally establish non-inferiority, regimen 5 holds promise as an alternative for patients unable to receive other recommended treatments.
- Conclusion: The trial found three new drug regimens that can deliver similar efficacy and safety to conventional treatments while reducing treatment time by up to two-thirds. The endTB regimens represent important alternatives for short MDR-TB treatment and complement the use of another highly effective, shorter MDR-TB regimen, called BPaLM, which is not suitable for certain populations. In addition, the trial supports the use of a fourth regimen as an alternative for people who cannot tolerate bedaquiline or linezolid; at least one of these two drugs is in every current World Health Organization-recommended regimen for MDR-TB.
Estimating the burden, mortality and morbidity of tuberculosis meningitis in children – a modelling study
- Background: Tuberculous meningitis (TBM) in children is universally fatal if untreated and can cause life-long disability for survivors. Yet, limited surveillance data are available with no estimates of the global burden of childhood TBM.
- Results: An estimated 21,300 (95% credible interval [CrI]: 15,800-28,200) children <15 years developed TBM in 2019, around 2% of the estimated TB incidence among children. Amongst children with TBM, an estimated 14,300 (95%CrI: 10,400-18,900) died – most <5 years old. Over 80% of children who died did not receive TB treatment; 7.5% (95%CrI: 7.0-7.9) of deaths were among children living with HIV. Of the survivors, 4,700 (95%CrI: 3,400 to 6,300) suffered neurological sequalae.
- Conclusions: These are the first estimates of childhood TBM, demonstrating high mortality and morbidity. TBM prevention strategies such as BCG vaccination and TB preventive therapy should be prioritised. Healthcare workers in high TB burden countries should have a high index of suspicion to facilitate early diagnosis and treatment.
- Summary: There is a paucity of surveillance data for tuberculous meningitis (TBM), the deadliest form of childhood tuberculosis. This modelling study provides the first global estimates of childhood TBM incidence, mortality and morbidity. Quantifying disease burden and outcomes are a critical first step towards addressing this crippling disease.
Subclinical drug-resistant tuberculosis missed by Xpert MTB/RIF in a rural South African community
- Background: Subclinical tuberculosis (TB) comprises up to half of prevalent pulmonary TB globally. The relevance of this to transmission of drug-resistant organisms is unknown.
- Methods: Between 2018-2020, we conducted a community-based survey to characterize infectious and non-communicable diseases in a health and demographic surveillance area in rural KwaZulu-Natal, South Africa. For participants who reported any of the four WHO TB screening symptoms or had any chest x-ray abnormality, we collected sputum for Xpert MTB/RIF Ultra (Xpert), MGIT liquid culture (MGIT) and phenotypic drug sensitivity.
- Findings: Among 18,041 screened individuals, 174 (1.0%) had newly diagnosed microbiologically-confirmed TB, defined as either Xpert or MGIT positive sputum. Of these 82% (143/174) were asymptomatic according to the WHO 4 symptom screen and were defined as subclinical TB. Compared to people with symptomatic TB, those with subclinical TB had a similar Xpert cycle threshold(median 27.9 vs 28, p=0.8) and similar days to MGIT positivity (16.4 vs 15.3, p=0.8). Of those with microbiologically-confirmed TB, 10% (18/174, Figure 1, left) had phenotypic drug resistance with no difference by symptom status (6.5% of symptomatic TB vs. 11% of subclinical TB, p=0.4). Of the 18 drug-resistant isolates characterized (Figure 1, right), 88.9% (16/18) were from subclinical TB, 50%(9/18) were multi-drug resistant (MDR) and 11.1% (2/18) were pre-extensive resistant (pre-XDR). 13/18 (72.2%) had phenotypic evidence of rifampin resistance, but only 3/13 (23.1%) of these were identified by Xpert.
- Conclusions: Individuals with subclinical, microbiologically-confirmed TB had similar bacterial burden and frequency of drug resistance as those with symptomatic TB. Eighty percent of rifampin-resistant strains were found in people with subclinical TB and three-quarters of these were “missed” by Xpert test. These findings highlight a substantial reservoir of drug-resistant TB that is unlikely to be detected by current, passive case-finding strategies.