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9th December 2024
The World Health Organization (WHO) has raised the alarm about soaring cases of tuberculosis (TB) around the world.
Last year, more than eight million people were newly diagnosed with the condition, the highest number since monitoring began in 1995, WHO said.
While TB-related deaths did fall last year from 1.32 million to 1.25 million, the total number of people falling ill with TB rose, a report said.
This means the world is not on track for international targets to reduce the burden of TB by 2027 and elimination by 2035, it added.
There is also ongoing concern about multidrug-resistant TB which the WHO described in the report as a ‘public health crisis’.
Treatment success rates for multidrug-resistant or rifampicin-resistant TB have now reached 68%.
But, of the 400 000 people estimated to have developed it, only 44% were diagnosed and treated in 2023, the report found.
Global funding for TB prevention and care decreased further in 2023 and remains far below target, it added with low- and middle-income countries bearing 98% of the TB burden.
India (26%), Indonesia (10%), China (6.8%), the Philippines (6.8%) and Pakistan (6.3%) together accounted for 56% of the global TB burden, it said.
Earlier this year, the UK Health Security Agency (UKHSA) said it was investigating an 11% rise in TB cases in England.
There were 4,850 tuberculosis cases in 2023 compared to 4,380 in 2022, representing a jump of 10.7%, according to provisional data.
Even before the Covid-19 pandemic, TB incidence was lower than this, with 4,615 cases in 2018 and 4,725 cases in 2019, UKHSA figures showed.
Some of the increase related to people born outside the UK, but in 2023 the rise was also seen in UK-born individuals, they noted.
Speaking on the findings of the latest WHO report, Dr Tereza Kasaeva, director of WHO’s Global Tuberculosis Programme said there was a multitude of formidable challenges including ‘funding shortfalls and catastrophic financial burden on those affected, climate change, conflict, migration and displacement, pandemics and drug-resistant tuberculosis, a significant driver of antimicrobial resistance’.
WHO director-general Tedros Adhanom Ghebreyesus added: ‘The fact that TB still kills and sickens so many people is an outrage, when we have the tools to prevent it, detect it and treat it.’
Dr Esther Robinson, head of the TB Unit at UKHSA, is encouraging people to speak to a healthcare professional if they think they could be at risk of TB.
‘TB is curable and preventable, but the disease remains a serious public health issue in the UK,‘ she said.
‘It is very important that those with relevant symptoms are tested for TB and appropriate treatment is started promptly. Not every persistent cough, along with a fever, is caused by flu or Covid-19.
‘A cough that usually has mucus and lasts longer than three weeks can be caused by a range of other issues, including TB.’
A version of this article was originally published by our sister publication Pulse.
11th September 2024
A new study has shown children and adolescents with immunocompromise who contract tuberculosis (TB) experience increased rates of non-respiratory TB and more severe forms of the disease, leading to a higher incidence of associated long-term health complications.
The study also revealed that standard immune-based TB detection tests are not accurate in immunocompromised children and therefore the researchers highlight a need to design prevention and management plans for these children who contract TB to minimise later health issues.
The researchers conducted a retrospective, multicentre, case-control study within the Pediatric Tuberculosis Network (pTBnet) European Trials Group. All participants were aged under 18 and had been treated for or diagnosed with TB at a European centre between 2000 and 2020.
Of the 417 TB cases included, 139 were immunocompromised, including those with human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions. A control group of 278 non-immunocompromised patients with TB was also included. All data was sourced from the pTBnet database.
Increased rates of non-respiratory TB were found in immunocompromised children compared to controls (32.4% vs 21.2%), and these patients had an increased likelihood of presenting with severe disease (57.6% vs 38.5%).
These children also had significantly higher rates of false-negative tuberculin skin test (31.9% vs 6.0%) and QuantiFERON-TB Gold assay (30.0% vs 7.3%) results at diagnosis. However, the microbiological confirmation rate was similar in immunocompromised and control cases (58.3% vs 49.3%).
Overall, the mortality rate of immunocompromised children was low (<1%), but the rate of long-term health complications resulting from the TB infection was significantly higher in immunocompromised children versus children in the control group (14.8% vs 6.1%).
To improve the long-term health outcomes and decrease the severity of the infection for immunocompromised children, the researchers suggest that future studies focus on better immune-based tests to diagnose TB in these children effectively.
In addition, the researchers emphasise the need for a better understanding of why immunocompromised children have an increased rate of associated long-term health so these children can be better managed at diagnosis and prevention strategies can be put in place to improve outcomes.
Reference
Rodríguez-Molino, P et al. Tuberculosis Disease in Immunocompromised Children and Adolescents: A Pediatric Tuberculosis Network European Trials Group Multicenter Case-control Study. Clinical Infectious Diseases 2024; Jul 15: doi.org/10.1093/cid/ciae158.
7th August 2024
Using one of the most detailed analyses ever undertaken into biological markers for tuberculosis (TB), researchers at the UK’s University of Southampton, working with colleagues from across the world, have identified a group of six biomarkers to help diagnose patients. Speaking to Katherine Price, lead author Dr Hannah Schiff shares her ambitions for these findings to pave the way for new lateral flow tests to diagnose more people with TB, diagnose them earlier and stop the infection from spreading.
Tuberculosis (TB) is the world’s deadliest infectious disease, killing more than one million people each year. An estimated 10.6 million people fell ill with TB in 2022, according to the World Health Organization (WHO). A disease often associated with health inequality, risk factors include smoking, alcohol abuse, HIV infection and malnourishment.
Europe accounted for 2% of all cases, according to the WHO data, and here it remains a public health issue despite most countries being low incidence. This is due to it predominantly affecting vulnerable populations such as migrants, prison inmates and people coinfected with HIV. In England, nearly 5,000 cases were recorded in 2023, with cases on the rise.
Closing diagnosis gaps is key in reducing incidence. However, in 2021, there were an estimated 3.7 million missed cases globally. Diagnostic delays, particularly in low- and middle-income countries, and funding for prevention, diagnostics and treatment fell far short of the globally estimated need and UN targets.
Treatment success rates in Europe also remain far below regional targets, and have in fact decreased, indicating increasing challenges to delivery of care. Up to half of patients do not complete treatment courses, according to one US study, which often last several months or even years for multidrug-resistant TB, even if they do get a diagnosis.
‘That’s the driver, to try and close that case-diagnosis gap and finding the missing millions,’ says Dr Hannah Schiff, a National Institute for Health and Care Research (NIHR) academic clinical lecturer and speciality registrar in respiratory medicine at the University of Southampton. She is also the lead author on a new study that has identified tuberculosis-specific diagnostic biological markers.
Fascinated with the lungs, Dr Schiff trained at the John Radcliffe Hospital in Oxford and the Royal Berkshire Hospital in Reading, UK, before embarking on her specialist respiratory training at Southampton. ‘They’re just an amazing body organ to study,’ she says. ‘It’s such an interface for infection and I’ve always been interested in infections and the host and pathogen interaction. Why does the same bug cause slightly different disease in different people? And TB is a case in point for that – there are so many host factors that alter how lung disease manifests.’
Currently, TB diagnosis commonly relies on sputum samples, which not all patients can produce, as well as the necessary infrastructure and skilled operators for analysis. Patients with TB can also have a negative sputum smear microscopy and culture result – the latter of which can take several weeks to return, and these approaches haven’t changed for decades, says Dr Schiff.
While molecular testing for TB DNA has emerged over the last decade, this also relies on sputum samples and therefore suffers from the same limitations.
‘Making the diagnosis is the biggest block to the entire care cascade, and once a diagnosis is made, then you’re most of the way there,’ she explains.
Dr Schiff and her colleague, senior author Professor Paul Elkington, developed their research to address the urgent need for accurate point-of-care testing that doesn’t rely on sputum expectoration or specialist equipment.
Their latest study, supported by the NIHR and UK Medical Research Council and published in the Journal of Clinical Investigation Insight, shows the potential for host proteins to support diagnostics. It was a team effort drawing on global expertise.
From the NIHR Southampton Biomedical Research Centre, senior author Dr Diana Garay-Baquero, a chemist originally from Colombia, led the proteomics work under the supervision of US-based proteomics expert Dr Spiros Garbis.
Dr Naomi Walker, infectious disease specialist and a researcher at the Liverpool School of Tropical Medicine, contributed a cohort of South African samples, and Marc Tebruegge in Vienna contributed a UK-based cohort. Bioinformatics data collection was overseen by the University of Southampton’s Dr Andres Vallejo and US-based Dr Christopher Woelk, while the University of Oxford supported with the validation phase. The study was also undertaken with experts from South Africa’s University of Cape Town and Cayetano Heredia University in Peru.
‘It was really inspiring to work with people globally [who] just have such a variety of background experience and can bring so much to the project,’ says Dr Schiff.
The academics used a proteomics technique that doesn’t remove albumin, which Dr Schiff says can inadvertently remove proteins of biological interest. The team believes it’s one of the most detailed analyses ever undertaken of biomarkers for TB.
Proteins are excellent candidates for diagnostic biomarkers, being stable and utilisable for near-patient diagnostic tests. However, while several studies have explored the potential of host plasma protein biomarkers for TB diagnosis, and numerous candidate proteins have been detected, biomarkers or combinatorial biomarker signatures had not yet been found that could reliably differentiate TB from other respiratory diseases or predict progression.
Dr Schiff and her team of researchers applied a highly sensitive non-depletion tandem mass spectrometry discovery approach and bioinformatic analysis. Using linear modelling and network correlation analyses, they identified 118 differentially expressed proteins. These were then narrowed down to six that could distinguish contagious TB from healthy controls and other respiratory infections.
The researchers hope these six blood proteins will pave the way for the development of an affordable, sensitive, specific, user-friendly and rapid point-of-care test that could be used in resource-limited settings. Dr Schiff says this could be particularly helpful for case finding and reducing TB rates in communities of high disease instance.
However, next steps will be largely dependent on funding, and she says the next realistic milestone will probably be at least a few years down the line.
‘At the moment, measuring the markers needs sequencing and very highly specialised laboratory equipment,’ she explains. ‘We’re planning experiments to do it in a lower-level lab facility with more standard equipment… to try and get it onto a device that could be used at point-of-care.’
The idea is to leverage diagnostics innovation that emerged during the Covid-19 pandemic, such as at-home lateral flow testing. ‘The dream would be if you could get these markers onto a lateral flow test. That would be ideal, but you need a device that can measure several markers, not just one, and with enough sensitivity and a semi-quantitative readout, not just a yes/no answer,’ adds Dr Schiff. ‘But if we could translate this into use in the field, that’s where it would have the most benefit.’
This could then help close the case-detection gap that fuels the global TB pandemic. ‘There shouldn’t be people in this world that are suffering from a disease that is curable and treatable, just for want of a diagnosis,’ says Dr Schiff.
Dr Schiff is currently working on further analysis of the proteomic datasets to explore variation of protein markers by host phenotypic characteristics and how these might be harnessed to improve diagnostic sensitivity.
Her colleague Dr Liku Tezera, who worked on the biomarker research, has developed a 3D TB infection cell culture model, which could be used to look at some of the identified biomarkers and explore their potential pathological role in TB infection, Dr Schiff explains. The TB clinic is also continuing to source samples from patients with active pulmonary disease, with help from a TB nursing team.
Wider developments in scaling up shorter treatment regimens, meanwhile, are believed to be behind the success rates for rifampicin-resistant TB that are slowly but consistently improving in Europe.
‘The key is having healthcare system support, your TB nursing team, and lines of communication and support open with the patients,’ says Dr Schiff. ‘We know what drugs work and we know the regimes. The challenges are getting people a timely diagnosis and successfully through the whole course of treatment.’
20th March 2023
Tuberculosis treatment in those with rifampin susceptible disease with an initial 8-week course containing bedaquiline and linezolid is non-inferior to the standard regimen, with respect to clinical outcomes, according to the TRUNCATE-TB trial investigators.
According to the World Health Organisation, in 2021, globally, an estimated 10.6 million people contracted tuberculosis, leading to an estimated 1.6 million deaths. Currently, treatment of drug susceptible pulmonary tuberculosis requires a 6-month rifampin-based regimen although this can affect adherence and ultimately lead to treatment failure. However, emerging evidence suggests that a 4-month rifapentine-based regimen containing moxifloxacin was non-inferior to the standard 6-month regimen. In the current study, researchers wondered if an initial 8-week treatment regimen, which could be extended for persistent clinical disease with follow-up after treatment and prompt re-treatment for those who relapse, may be as effective as the current standard regimen.
The Two-Month Regimens Using Novel Combinations to Augment Treatment Effectiveness for Drug-Sensitive Tuberculosis (TRUNCATE-TB) trial, compared whether an initial regimen of either high-dose rifampin-linezolid or bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol) was non-inferior to the current standard regime of rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks. Individuals were randomised to either the standard regime or a strategy of an 8-week regimen (rifampin-linezolid or bedaquiline-linezolid) with extended treatment if required. The primary outcome was a composite of death, ongoing treatment, or active disease at week 96 and the non-inferiority margin set at 12%.
Tuberculosis treatment strategy outcomes
A total of 674 participants were included and randomised to the different strategies.
The primary outcome event occurred in 3.9% of those in the standard regime and 11.4% in the rifampin-linezolid regimen (adjusted difference, AD = 7.4%, 95% CI 1.7 – 13.2%), hence non-inferiority was not met. In contrast, the primary outcome occurred in 5.8% of those assigned to bedaquiline-linezolid regimen (AD = 0.8%, 95% CI -3.4 to 5.1%), hence the criterion for non-inferiority (12%) was met with this regimen.
In fact, the mean total duration of treatment was 180 days in the standard-treatment group but only 85 days in the bedaquiline-linezolid strategy group, with a similar incidence of grade 3 or 4 adverse and serious events across the three groups.
The authors concluded that use of an 8-week regimen with bedaquiline-linezolid proved to be non-inferior to the standard regimen and with no apparent safety concerns.
Citation
Paton NI et al. Treatment Strategy for Rifampin-Susceptible Tuberculosis. N Eng J Med 2023
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