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Breathing In A Deadly Dust: How A Drop Of Blood Can Help

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Is England On Track For A Healthy Cattle Herd And TB-free Future?

Bovine TB is a devastating disease affecting cattle, causing significant trauma for livestock farmers and rural communities.

It is the most challenging animal health disease the UK faces, costing taxpayers tens of millions of pounds each year.

In 2011, Defra spent £95m battling it – almost 40% of its entire animal health and welfare budget of £220m.

See also: Bovine TB cattle slaughterings in England lowest in 15 years

There was a stark realisation from within government and the industry that something needed be done.

In July 2013, under the Conservative and Liberal Democrat coalition government, then-Defra secretary Owen Paterson set out his plan to rid England of bovine TB in 25 years.

Launching the strategy, Mr Paterson said 28,000 otherwise healthy cattle had been slaughtered in the UK in the previous year because of TB.

The minister explained he had visited Australia, New Zealand, Ireland and the US, and the country "must learn from their successful eradication programmes".

The strategy was developed by the Animal Health and Welfare Board for England (AHWBE) and the Bovine Tuberculosis Eradication Advisory Group for England (TBEAG).

It drew extensively on experiences in the four countries visited by Mr Paterson, all of which successfully tackled bovine TB by addressing the disease in cattle and in wildlife.

Michael Seals, then chairman of the AHWBE, recalls being asked by farming minister Jim Paice to create the consultation document that led to the policy.

"The biggest impact was the realisation something dramatic had to be done," says Mr Seals.

"We just couldn't go on as we were – testing and removing cattle was not an option. There had to be action on wildlife."

Various workshops involving many people affected by the disease were held across the country.

The work within Defra was taken up by TBEAG, led by John Cross, who brought together the experts necessary to achieve a good co-design policy proposal.

Multi-pronged approach

Behind the scenes, there was a lot of interest in developing the policy beyond the badger cull, including exploring the possibility of cattle vaccination and the requirement for an associated detecting infected among vaccinated animals (Diva) diagnostic test.

World-renowned bovine TB expert Prof Glyn Hewinson and a team from the Animal and Plant Health Agency were looking at the science of TB, including badger and cattle vaccination, PCR testing of badger faeces and the desire to find a more reliable and accurate cattle test.

Oral BCG vaccination of badgers was considered to be the "holy grail", but despite many trials, this remains unachievable.

Defra devised the badger culling policy in conjunction with stakeholders including the NFU, which paid for a lot of the administrative costs and the setting up of the culling companies.

"It was a joint enterprise – working to achieve a common good," says Mr Seals.

Badger culling was supposed to start in England in autumn 2012, but it was delayed after the Badger Trust launched a legal challenge at the High Court in London.

This was unsuccessful and the policy was introduced in two pilot counties in the summer of 2013 – Gloucestershire and Somerset.

Licensed culls carried out by trained marksmen have since been rolled out to 72 areas of England.

In the long term, however, government policy seeks to replace culling with vaccination, both of cattle and badgers.

Cattle vaccination trials

Sarah Tomlinson is a Derbyshire-based farm vet and technical director of the Defra-funded TB Advisory Service (Tbas), which since 2017 has delivered more than 3,000 farm visits to livestock farms in England to tackle TB.

She says: "I believe that the success of the first 10 years of the eradication stage is down to a combination of policies.

"In order to achieve TB freedom by 2038, we need to embrace the new science and technology that is advancing all the time.

"For example, the current trials to allow the delivery of a cattle BCG vaccination programme and the associated Diva skin test. Hopefully, one day, there will be a TB-free future for wildlife, cattle and our farmers."

Bovine TB strategy in the devolved regions

Agricultural policy is devolved, which explains why each nation has a different eradication strategy and target.

In Wales, the Welsh government has a goal of eradicating bovine TB by 2041.

The Labour minority administration announced a "refreshed" five-year plan in March, with a policy focused on cattle measures.

NFU Cymru has criticised the plan for its lack of focus on tackling the disease in wildlife, in particular badgers.

In Northern Ireland, former farm minister Edwin Poots launched a long-term Bovine TB Eradication Strategy in March 2022 in collaboration with the TB Eradication partnership, industry and stakeholders.

The wildlife intervention part of the strategy is subject to legal challenge, with the outcome of a judicial review expected soon.

Scotland is officially TB-free and its control measures are centred around trade.

Sir Jim, who farms a small fold of pedigree Highland cattle in the Newmarket area, says there is still a long way to go to achieve TB-free status.

"I'm a bit concerned about the direction of the strategy. I think Defra should leave the option open [of badger culling]. Although there may well be a change in government with a different policy," he adds.

Cheshire-based dairy farmer Phil Latham, who is also a member of the Bovine TB Partnership, says whichever government is in power must ensure future TB policy is "based on the science and evidence, and not politics".

"My concern would be allowing the regrowth of the badger population in the absence of proven new tools," he adds.

"There is no evidence to prove that vaccination of badgers or cattle reduces cattle TB. It appears that politics, not evidence, is driving future policy."

View from experts

Prof Hewinson, who is now Sêr Cymru research chairman in the Centre of Excellence for Bovine Tuberculosis for Wales at Aberystwyth University, says good progress has been made in England by addressing all the sources of TB infection.

He believes further progress will require more focus on understanding the local drivers of TB transmission and applying the most appropriate interventions at a local level.

"What we are really trying to do is reduce the basic reproduction rate for TB, R0, below one so that it dies out," Prof Hewinson says.

"This is best achieved through a multi-pronged approach, using the best tools at our disposal in the right place at the right time, making marginal gains along the way. Sadly, there is no magic bullet."

James Wood is an experienced veterinary epidemiologist at the University of Cambridge who works on bovine TB in the UK, Ethiopia and India.

He says scientists now have a much better understanding of TB than they did 10 years ago, which is helping to formulate better evidence-based policy.

"Fifteen years ago, people were focusing on badgers, but it's really good to see cattle measures are being recognised as important.

"Likewise, it is important to recognise there are big changes associated with badger culling. We're moving away from the concept of there being one silver bullet. We are trying to tackle TB on all fronts."

Government response

Defra says there are signs its strategy is working. Latest data shows the percentage of cattle herds under TB restrictions in England (prevalence) is, at 4.3%, one of the lowest since October 2010, having peaked at 6.4% in March 2018.

But the department insists now is the right time to transition its policy from blanket approaches to more targeted interventions across England.

UK chief vet Christine Middlemiss says: "We have always been clear that we do not want to continue the current badger cull longer than necessary.

"Our bovine TB eradication strategy has led to a significant reduction in this insidious disease and building on the progress made, we are now able to move onto the next phase, including wider badger vaccination, alongside improved cattle testing and working towards deployment of a cattle vaccine."

TB conferences round-up

The TB Advisory Service (Tbas) is hosting the second National TB Conference at Sixways Stadium, Worcester, on 29 November 2023.

The Defra-backed event aims to reflect on the 10 years of the TB Eradication Scheme for England, and look forward to what the next 15 years may bring, asking: "Is TB freedom really a possibility by 2038?"

Hosted by Tbas technical director Sarah Tomlinson, it will include five technical presentations and two question-and-answer panel sessions.

There will be exhibitor stands and opportunities for delegates to network, discuss topics with speakers and catch up on the latest TB updates. For further information and ticketing, visit www.Tbas.Org.Uk.

Meanwhile, the annual AberTB conference will take place on 13 September at Aberystwyth University. This year's topic is TB in wildlife. Tickets are available at shop.Aber.Ac.Uk.


Study Explores Lipid And Metabolic Alterations In HIV/TB Co-infected Patients

In a recent study published in the BMC Infectious Diseases, a group of researchers investigated the differential impact of human immunodeficiency viruses (HIV)/ tuberculosis (TB) co-infection on lipid and metabolic profiles.

Study: The metabolic consequences of HIV/TB co-infection. Image Credit:Jarun Ontakrai/Shutterstock.Com Background

HIV-positive individuals face a significantly high level of risk of developing active TB due to HIV's immunosuppressive effects. TB ranks as the predominant secondary infection among this demographic, intensifying the global issue of HIV/TB co-infection. The coronavirus disease 2019 (COVID-19) pandemic has further strained healthcare accessibility, worsening the diagnosis and treatment of both diseases and boosting TB-related fatalities.

The interplay between HIV and TB worsens the host's health due to combined immune system degradation and induces metabolic dysfunction. Metabolic changes in co-infected patients are not fully understood, but initial studies using advanced techniques like two-dimensional gas chromatography time-of-flight (TOF) mass spectrometry promise deeper insights. Further research is required to enhance the understanding and treatment of HIV/TB co-infection.

About the study

In the present study, serum samples collected by the South African TB Vaccine Initiative (SATVI) and the Desmond Tutu HIV Centre were cryopreserved at -80°C and later sent to North-West University for analysis.

Participants were South African adults from specific regions in Cape Town, aged between 18 and 69 years. Samples were categorized based on HIV and TB status and treatment.

The researchers analyzed the metabolic profiles of several participant groups: healthy controls, untreated HIV-negative TB-positive individuals, untreated HIV/TB co-infected individuals, and treated HIV/TB co-infected individuals. The main aim was to distinguish the effects of the infection from treatment effects, aiding in future medical interventions.

Samples underwent extraction and derivatization and were analyzed using a gas chromatographer-mass spectrometer, and the obtained data was further processed using ChromaTOF software.

The study adopted various statistical tests to identify key metabolites. Analyses included t-tests, fold change, ANOVA, principal component analysis, and hierarchical clustering analysis. Adjustments for missing values and multiple testing corrections were incorporated to ensure accuracy.

Study results

The study revealed that after examining various compounds, 529 were initially detected. However, post-data cleaning, many significant metabolites could not be annotated due to issues like low signal-to-noise ratios, unsuccessful deconvolution, or library absence.

Unlinked metabolites were labeled "exogenous/unannotated" and left undiscussed, suggesting their roles in human serum need more investigation.

Notably, two samples from the untreated co-infected group had unusually high clusters of differentiation 4 (CD4) T-cell counts. During hierarchical clustering, these samples clustered with healthy controls, indicating no major metabolic disruption from their dual infections.

Another observation was that when untreated patient samples were compared using t-tests, no metabolites showed significant differences after multiple test corrections. However, six metabolites had noteworthy probability (p)-values when not accounting for false discovery rates.

These metabolites seem to correlate with CD4 T-cell counts, as they were diminished in the group, showing a severe disease state based on these counts.

Comparisons between untreated patient samples and healthy controls indicated partial overlap in metabolic profiles. Certain metabolites were either significantly increased or decreased in untreated patients relative to healthy controls.

Further analysis of all groups showed no clear metabolic distinction between healthy and patient groups. However, patients on antiretroviral therapy (ART) displayed distinct metabolic shifts, suggesting ART's influence on metabolism. Out of various differentiating metabolites, several are involved in lipid metabolism, reflecting typical HIV infection profiles.

Discussions

In the present study of metabolic profiles in HIV/TB co-infection, there was an overlap with TB-only metabolic signatures, yet unique characteristics emerged. The complexity of the human metabolome still requires further exploration.

The results point to significant metabolic changes in those with the co-infection. Further, it was found that certain metabolites related to lipid and protein metabolism were observed to decrease, suggesting an advanced stage of disease in those with a lower CD4 T-cell count.

Additionally, cholesterol metabolism plays a role, particularly in relation to CD4 T-cell counts. Another observation includes decreased leucylleucine, which goes against expectations but suggests a depletion of protein reservoirs in co-infected individuals.

The breakdown of proteins, a hallmark of HIV and TB infection, became evident through the elevation of specific metabolites. These metabolic alterations point to a low energy state and a possibly disrupted gut microbiome due to chronic inflammation from these diseases.

Comparing untreated HIV/TB co-infected groups to TB-only groups revealed altered phenylalanine and tryptophan levels. This could be attributed to immune responses from HIV infection. Tryptophan metabolism, influenced by gut microbiota, has decreased levels in co-infected groups, suggesting its potential as a biomarker for co-infection.

The lipid-related metabolites decreased more in the HIV/TB co-infected group than in the TB-only group. This emphasizes HIV's role in changing lipid metabolism and agrees with the results of other studies.

Glycerol-3-phosphate plays a critical role in energy production in the brain and muscles, connecting fatty acid metabolism with energy processes. Important polyunsaturated fatty acids like alpha-linolenic acid and arachidonic acid are critical for cell structures and inflammation mediation. Notably, low alpha-linolenic acid can lead to unchecked virus proliferation.

In the untreated co-infected group, lower levels of dodecanal were found, highlighting the potential role of decanoic acid as an energy source. This change hints at membrane alterations seen in past HIV research. Lipids crucial for structural and immunity functions were also affected.

Fatty acids like 3,4-dihydroxybutyric acid (DHBA) were elevated in the co-infected group, pointing to health and nutritional issues often seen in HIV and TB patients. Its presence correlates with increased inflammation and microbial shifts, highlighting the direct implications of gut microbial metabolism for human health.

Certain microbial byproducts, previously elevated during HIV, decreased in co-infected groups, possibly due to HIV's impact on gut health. ART treatment, while beneficial, does not restore metabolic balance completely and might still foster inflammation. Some metabolic changes specific to ART-treated individuals might be due to ART's mitochondrial effects.






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