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‘THE TIME FOR THE GLOBAL TB COMMUNITY TO ACT IS NOW’ - NEW RESEARCH SHOWS FAILURE OF CURRENT POLICIES TO ERADICATE TB

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The Union World Conference on Lung Health 2023 - Friday 17 November press release

  • Research breakthroughs presented at The Union World Conference for Lung Health include findings that current policies could leave half of TB transmission missed;
  • World Health Organisation launches new roadmap to prevent and treat childhood TB;
  • New approach to TB case finding in Cambodia increases detection by 370%;
  • Smoking leads to accelerated ageing in young smokers compared to older smokers;
  • Scientists make new discoveries linking adolescent TB to infertility if left untreated.

Watch the press conference on YouTube.

Paris; November 17th 2023: Researchers from the London School of Hygiene and Tropical Medicine has suggested that half of TB transmission occurs before individuals will even access care under existing TB care policies.

This investigation suggests that one in two individuals with subclinical TB, who are likely infectious but are not aware of symptoms, will not progress to disease severe enough to seek care.

Research presented on day three of The International Union Against TB and Lung Disease’s World Conference on Lung Health revealed how new insights into TB highlight the weakness of current policies designed to eradicate the disease, where individuals need to report symptoms in a clinic before receiving care.

The amount of transmission missed was reduced to a third if the study assumed a lower relative infectiousness for subclinical TB.

The study, which used a deterministic modelling framework based on 1,000 cohorts of 10,000 individuals, found that 93.5% of TB-infected individuals will not contribute to transmission within 10 years of MTB infection.

Prof Rein Houben, Principal Investigator of the European Research Council funded project said: “The TB community has suspected for a while that current TB policies are not enough to drive TB down. Our work maximised the value of old and new data using mathematical models, and while still in development our results show just how much transmission is missed, and how many individuals with likely infectious TB will not receive care.”

TB CASES NEED TO BE ACTIVELY SOUGHT OUT TO REDUCE TRANSMISSION

At The Union World Conference, tuberculosis experts also presented how active case finding (ACF) could reduce the 52,000 TB cases in Cambodia, of which nearly 50% go undiagnosed. With this figure often higher in minority and hard-to-reach communities, scientists stressed the importance of focusing ACF efforts in these areas.

Researchers conducted mobile case findings across 26 remote communities, which resulted in over 8,000 patients being screened.  More than 5% of these people were diagnosed with TB – with 321 TB patients receiving treatment that they would not have otherwise, constituting an increased detection of 370%.

These results demonstrated the positive impact of adopting a policy of ACF in reducing transmission of TB within the community, coupled with widening invaluable access to diagnostic facilities.

WORLD HEALTH ORGANISATION SHARES PROJECT FOR ENDING CHIILDHOOD TB

The urgency of researchers’ findings was reflected by the launch of the World Health Organisation’s roadmap to prevent and treat TB in children and adolescents. The roadmap outlines an ambitious five-year plan with 10 key actions to improve the prevention, treatment, and care of TB in young people.

Children and adolescents experience a disproportionate burden of TB. The WHO recently released its Global Tuberculosis Report, which highlighted that an estimated 1.25 million children and young adolescents fell ill with TB in 2022, making up 12% of the global TB burden.

“It is unacceptable that hundreds and thousands of children and adolescents worldwide still do not have access to life-saving TB prevention, treatment and care”, said Dr Tereza Kasaeva, Director of WHO’s Global TB Programme.

“The new Roadmap lays the groundwork for much needed actions over the next five years building on commitments made by world leaders at the 2023 UN High Level Meeting on TB, to close gaps in access to care and safeguard the rights of children and adolescents.”

SMOKING ACCELERATES CELL AGEING IN THE YOUNG

Pakistani researchers, led by Uzair Abbas from Aga Khan University, reported an “alarming” discovery that chemical compounds in cigarette smoke also accelerate cell ageing, with this process occurring more quickly in younger smokers than those who are older.

The impact of smoking on lung health contributes globally to about 6 million deaths per year worldwide. Beside the impact of smoking on lung health, this study suggests that younger smokers are more susceptible to changes in their cell physiology, potentially leaving them at a greater risk of developing poor oral and lung health.

LONGER-TERM IMPACTS ON FERTILITY OF TB DIAGNOSES IN THE YOUNG REVEALED

Additional research conducted by New Delhi-based researcher Dr Sangeeta Sharma from India’s National Institute of Tuberculosis and Respiratory Diseases exposed the shocking long-term impacts that TB can wreak in young patients through research into the effects of pulmonary TB (PTB) in adolescent girls. PTB is a common form of TB which involves an infection of the lungs.

In adolescent girls, the disease can cause menstrual dysfunction and the formation of tubo-ovarian masses, which can lead to infertility later in life.

The study examined 280 adolescent girls with PTB, with a shocking 15% of these found to have TB-related genital findings, and 12% to have tubo-ovarian masses.  Patients with severe forms of the disease including drug resistant cases were affected more severely. However, early diagnosis and timely treatment could prevent permanent damage, Dr Sharma found.

As a global disease suffered by millions across the world, these potentially devastating longer-term effects of a PTB infection hammer home the vital importance of securing timely diagnosis and treatment.

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.

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.

Professor Guy B. Marks, President and (Interim) Executive Director, International Union Against Tuberculosis and Lung Disease (The Union) said: “The presentations given today at The Union World Conference on Lung Health have shown that the time for the global TB community to act is now. We must continue to keep broadening access to diagnostic and treatment of tuberculosis. Through further research, innovation, and education, we can ensure that no-one is left behind as we strive towards a world free of tuberculosis and lung disease.”

The Union

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.

ENDS

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 theunion@lexcomm.co.uk. 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 taking place at 13:30 CET, 17th November 2023. 

The Union social media:

Twitter: @TheUnion_TBLH

Facebook: The Union Lung Health

LinkedIn: International Union Against Tuberculosis and Lung Disease (The Union)

Overview of Each Abstract:

 

Smoking induces cellular ageing and over production of reactive oxygen species in oral mucosal cells

  •  Background: The World Health Organization (WHO) estimates a 21% prevalence rate of smoking across the world that leads to about 6 million deaths per annum globally. Chemical components in cigarette smoke have been proven to cause over production of Reactive Oxygen Species (ROS). ROS in turn, alters the cell physiology which can lead to multiple oral and pulmonary pathologies. We aimed to investigate the impact of smoking on the levels of ROS and its effects on cellular aging in oral mucosal cells.
  • Design/Methods: Oral swabs of 50 smokers and 50 nonsmokers were taken through cytology brush. The ROS were quantified by using 2'7' dichlorodihydrofluorescein-diacetate (DCFH-DA) dye through flow cytometry. For cellular aging, RNA was extracted from mucosal cells via TRIzol™ method and mRNA expression of cysteine-rich angiogenic inducer 61 (CYR61), a cellular aging marker, was compared through qRT-PCR. Data was analyzed in SPSS, with 95% C.I, p value < 0.05 was considered as significant.
  • Results: Smokers had higher percentage of ROS as compared to non-smokers (p value < 0.001). There was also over-expression of CYR61 gene as compared to non-smokers (p value= 0.001). While comparing ROS and cellular aging between young smokers and old smokers, surprisingly we found significantly higher % of ROS and up regulation of CYR61 gene expression in young smokers as compared to old smokers (p value 0.001 and <0.0001 respectively).
  • Conclusions: Smoking induces higher amount of ROS and cellular aging in oral mucosal cells. In young smokers, ROS and cellular aging were higher as compared to old smokers. This is alarming and might be leading cause of oral pathologies in the smoker.
  • Summary: In smokers, we found over production of reactive oxygen species and over expression of mRNA levels of CYR61- an aging related gene. moreover, this effect was seen frequently in young smokers as compared to old smokers which is an alarming situation.

 

Prevalence of genital in involvement and tubo-ovarian masses pulmonary TB in adolescent girls

  •  Background: Pulmonary TB (PTB) is common in adolescent girls and can cause involvement of genital organs, later on can causing infertility. The study aims to show the prevalence of genital involvement and tubo-ovarian masses in Pulmonary tuberculosis in an Adolescent girls.
  • Design/Methods: It was a observational cohort study on 280 adolescent girls aged between 10-17 years of age (mean 13.1 years) having pulmonary tuberculosis (PTB) and tubo –ovarian masses (TO masses). They were evaluated by transabdominal ultrasound or PET CT (Positron Emission Topography-Computed Tomography). It was done on selected number of cases to see the increase activity of glucose uptake.
  • Results: Out of 280 PTB adolescent girls, 42 (15%) had ultrasonic abnormalities in the form of tubo-ovarian masses in 34 (80.95%) (bilateral in 22 (52.38%), right sided 8(19%) and left sided in 4 (9.5%) cases. Other abnormalities were hydrosalpinx in 12 (28.57%), bilateral in 7(16.6%) and unilateral in 5 (11.9%), thin endometrium in 34 (80.95%), endometrial fluid in 18(42.8%), endometrial calcification in 2 (4.7%), endometrial synchiae in 4(9.5%), impaired endometrial vascularity in 12 (28.57%), ascites in 6(14.2%) and peritoneal omental thickening in 4 (9.5%) cases. Menstrual blood was positive for PCR in 18 (42.8%) cases but didn’t show AFB on microscopy or culture in any case. Figure 1 shows findings (A) F18 FDG-PET/CT study showing large cystic mass (arrow) with mildly increased FDG uptake (B) adnexal mass (arrow) with no FDG uptake. Subjects were treated with 6 months of ATT. USG and PET CT was normal in 38 patients (90.4%) but had persistent TO masses in 3 (7.14%) patients (without increase of FDG uptake) and uterine synchiae in 2 (4.7%) patients.
  • Conclusions: There is a high involvement of genital organs in pulmonary tuberculosis cases. Timely diagnosis and treatment can prevent permanent damage to genital organs thus can prevent future infertility.

 

 Targeted active case-finding should be prioritised in settings with low notification rates: lessons learnt from TB case-finding among minorities in Cambodia

  • Background: Cambodia's estimated TB burden is approximately 52,000 cases, while the NTP reported 30,017 notifications in 2019. It was demonstrated that there is still a large gap in case notifications (42%). Hard-to-reach minority communities mostly live without seeking health care when they face health problems.
  • Design/Methods: A mobile active case finding (ACF) was conducted in 26 remote communities in 3 operational districts (OD). Community leaders and local authorities were trained on how to screen for presumptive TB and refer to the mobile ACF that is set up at the center of each community. Mobile team set up ACF days at communities and screened people using a TB symptom questionnaire and chest X-ray. Those with a positive screening were then tested on the Xpert MTB/RIF assay.
  • Results: Across three rural ODs, 28 communities were visited by the mobile ACF team on ACF days, resulting in a screening of 8,348 presumptive cases by CXR. 1,190 (14%) were tested by GeneXpert, resulting in the detection of 214 Bac+. A total of 440 new TB cases in all forms were put on treatment. New TB case notifications increased by +370% during a semester of ACF compared to the five-year trend of expected notifications. This translates into an estimated 321 TB patients being treated who would not have received care in the absence of the ACF intervention.
  • Conclusions: Hard-to-reach population groups are often unaware of the extent of the TB intervention in their communities and the potential for ACF. In settings with low notification rates, targeted ACF interventions such as this should be prioritized to reduce the pool of prevalent TB patients.

Summary: Cambodia remains on the global TB watch list, and the path toward ending TB was impeded by the missing cases. Hard-to-reach minority communities living in remote areas are facing less access TB diagnosis and treatment. Bringing the service closer to the communities will increase service uptake and reduce TB infection.

 

Transmission pathways across the spectrum of TB disease – how much transmission are we missing?

  • Background: As new technologies are developed to diagnose and treat tuberculosis (TB) disease before individuals self-report to a clinic, it is key to understand how much transmission is left undiagnosed by current policies. Here we extended a data-driven, mathematical modelling approach to quantify different pathways through the spectrum of TB disease in terms of transmission contribution.
  • Design/Methods: We simulated 10-year pathways for 1,000 cohorts of 10,000 individuals using a deterministic modelling framework of Mycobacterium tuberculosis (Mtb) infection with progression and regression across minimal (pathological damage but not infectious), subclinical (pathological damage and infectious) and clinical (infectious and reporting symptoms) TB disease, acknowledging natural recovery, treatment, and mortality. Transition parameters were informed by historical and contemporary data, and subclinical disease was assumed 50% as infectious as clinical disease. We grouped individuals based on whether they contributed to transmission and whether or not they progressed to clinical disease. The main outcome was the proportion of all transmission attributable to each pathway group.
  • Results: We estimate that 93.5% (95% credible interval, CrI, 93.1-94.0) of Mtb-infected individuals will not contribute to transmission within 10 years of Mtb infection. 51.9% (95% CrI 48.4-55.7) of those that do contribute will never progress to clinical disease, driving over one third (35.5%, CrI 29.5-43.1) of all transmission over a 10 year period. This increased to 50.3% (95% CrI 42.0-61.2) if we assumed no difference in relative infectiousness for subclinical TB.
  • Conclusions: Our findings suggest that at least one third, and up to half, of transmission following Mtb infection comes from individuals who will never progress to clinical disease, and are left undiagnosed by current policies. If we are to End TB and halt transmission, TB care and prevention policies need to consider all infectious TB, not just who report to a clinic.